[ { "id": "https://authors.library.caltech.edu/records/t3k1f-dtw80", "eprint_id": 120139, "eprint_status": "archive", "datestamp": "2023-08-20 09:07:12", "lastmod": "2023-12-13 17:18:00", "type": "monograph", "metadata_visibility": "show", "creators": { "items": [ { "id": "Tan-Chieh-Hsiang", "name": { "family": "Tan", "given": "Chieh-Hsiang" }, "orcid": "0000-0002-5432-0160" }, { "id": "Cheng-Kai-Wen", "name": { "family": "Cheng", "given": "Kai-Wen" }, "orcid": "0000-0001-9888-9773" }, { "id": "Park-Heenam", "name": { "family": "Park", "given": "Heenam" }, "orcid": "0000-0001-7911-5828" }, { "id": "Sternberg-P-W", "name": { "family": "Sternberg", "given": "Paul W." }, "orcid": "0000-0002-7699-0173" }, { "id": "Chou-Tsui-Fen", "name": { "family": "Chou", "given": "Tsui-Fen" }, "orcid": "0000-0003-2410-2186" } ] }, "title": "LINKIN-associated proteins necessary for tissue integrity during collective cell migration", "ispublished": "unpub", "full_text_status": "public", "note": "The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. \n\nWe thank Barbara Perry, Wilber Palma and Stephanie Nava for laboratory assistance. We thank members of our laboratory for discussions. Mutant alleles- mvk-1(tm6628), trd-1(tm2764), vha-19(tm2225), prx-3(tm6469), and rod-1(tm6186) were provided by the MITANI Lab through the National Bio-Resource Project of the MEXT, Japan. Some strains were obtained from the Caenorhabditis Genetics Center (CGC), which is funded by the NIH Office of Research Infrastructure Programs (P40 OD010440). This work was also facilitated by WormBase, a knowledgebase for nematode research; and by the Alliance of Genome Resources, a research platform that facilitates cross species research, This research was supported by NIH R01HD086596 (PWS and TFC), R01HD091327 (PWS), and R24 0D023041 (PWS). \n\nThe authors have declared no competing interest.\n\n
Submitted - 2023.02.08.527750v1.full.pdf
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", "abstract": "Cell adhesion plays essential roles in almost every aspect of metazoan biology. Previously, using the developmental migration of the nematode male gonad as a platform, LINKIN (Human: ITFG1,C. elegans: lnkn-1), a relatively understudied transmembrane protein conserved across the metazoa, was found to be necessary for tissue integrity during migration. InC. elegans, loss of lnkn-1 results in the detachment of the lead migratory cell from the rest of the developing male gonad. Three interactors of ITFG1/lnkn-1-RUVBL1/ruvb-1, RUVBL2/ruvb-2, and alpha-tubulin were identified by proteomic analysis using the human HEK293T cells and validated in the nematode male gonad. The ITFG1-RUVBL1 interaction has since been independently validated in a breast cancer cell line model that also implicates the involvement of the pair in metastasis. In this study, we showed that epitope-tagged ITFG1 localized to the cell surface of MDA-MB-231 breast cancer cells. Using unbiased mass spectrometry-based proteomics, we identified a new list of potential interactors of ITFG1. Loss-of-function analysis of their C. elegans orthologs found that three of the interactors - ATP9A/tat-5, NME1/ndk-1, and ANAPC2/apc-2 displayed migratory detachment phenotypes similar to that of lnkn-1. Taken together with the other genes whose reduction of function phenotype is the same as LINKIN (notably cohesion and condensin) suggests the involvement of membrane remodeling and chromosome biology in the tight adhesion dependent on LINKIN, and support the hypothesis for a structure role of chromosomes in post-mitotic cells.", "date": "2023-03-21", "date_type": "published", "id_number": "CaltechAUTHORS:20230316-182235000.22", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20230316-182235000.22", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Ministry of Education, Culture, Sports, Science and Technology (MEXT)" }, { "agency": "NIH", "grant_number": "P40 OD010440" }, { "agency": "NIH", "grant_number": "R01HD086596" }, { "agency": "NIH", "grant_number": "R01HD091327" }, { "agency": "NIH", "grant_number": "R24 0D023041" } ] }, "local_group": { "items": [ { "id": "Division-of-Biology-and-Biological-Engineering" } ] }, "doi": "10.1101/2023.02.08.527750", "primary_object": { "basename": "media-3.xlsx", "url": "https://authors.library.caltech.edu/records/t3k1f-dtw80/files/media-3.xlsx" }, "related_objects": [ { "basename": "media-4.xlsx", "url": "https://authors.library.caltech.edu/records/t3k1f-dtw80/files/media-4.xlsx" }, { "basename": "media-5.docx", "url": "https://authors.library.caltech.edu/records/t3k1f-dtw80/files/media-5.docx" }, { "basename": "media-6.docx", "url": "https://authors.library.caltech.edu/records/t3k1f-dtw80/files/media-6.docx" }, { "basename": "2023.02.08.527750v1.full.pdf", "url": "https://authors.library.caltech.edu/records/t3k1f-dtw80/files/2023.02.08.527750v1.full.pdf" }, { "basename": "media-1.xlsx", "url": "https://authors.library.caltech.edu/records/t3k1f-dtw80/files/media-1.xlsx" }, { "basename": "media-2.xlsx", "url": "https://authors.library.caltech.edu/records/t3k1f-dtw80/files/media-2.xlsx" } ], "resource_type": "monograph", "pub_year": "2023", "author_list": "Tan, Chieh-Hsiang; Cheng, Kai-Wen; et el." }, { "id": "https://authors.library.caltech.edu/records/vv73j-vph14", "eprint_id": 120144, "eprint_status": "archive", "datestamp": "2023-08-20 09:04:21", "lastmod": "2023-12-22 23:45:05", "type": "monograph", "metadata_visibility": "show", "creators": { "items": [ { "id": "Wang-Grace-Z", "name": { "family": "Wang", "given": "Grace Z." }, "orcid": "0000-0002-0938-304X" }, { "id": "Warren-Elizabeth-A", "name": { "family": "Warren", "given": "Elizabeth A." } }, { "id": "Haas-Allison-L", "name": { "family": "Haas", "given": "Allison L." }, "orcid": "0000-0002-2154-4328" }, { "id": "S\u00e1nchez-Pe\u00f1a-Andrea", "name": { "family": "S\u00e1nchez Pe\u00f1a", "given": "Andrea" }, "orcid": "0000-0002-4843-3652" }, { "id": "Kiedrowski-Megan-R", "name": { "family": "Kiedrowski", "given": "Megan R." }, "orcid": "0000-0003-4610-182X" }, { "id": "Lomenick-Brett", "name": { "family": "Lomenick", "given": "Brett" }, "orcid": "0000-0002-5023-9998" }, { "id": "Chou-Tsui-Fen", "name": { "family": "Chou", "given": "Tsui-Fen" }, "orcid": "0000-0003-2410-2186" }, { "id": "Bomberger-Jennifer-M", "name": { "family": "Bomberger", "given": "Jennifer M." }, "orcid": "0000-0003-4767-6238" }, { "id": "Tirrell-D-A", "name": { "family": "Tirrell", "given": "David A." }, "orcid": "0000-0003-3175-4596" }, { "id": "Limoli-Dominique-H", "name": { "family": "Limoli", "given": "Dominique H." }, "orcid": "0000-0002-4130-337X" } ] }, "title": "Staphylococcal secreted cytotoxins are competition sensing signals for Pseudomonas aeruginosa", "ispublished": "unpub", "full_text_status": "public", "note": "The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. \n\nThis work was supported by the Jacobs Institute for Molecular Engineering for Medicine and the Center for Environmental Microbial Interactions at Caltech, and by the Institute for Collaborative Biotechnologies through cooperative agreement W911NF-19-2-0026 from the U.S. Army Research Office, the Cystic Fibrosis Foundation (LIMOLI19R3 to DHL and BOMBER18G0 to JMB), and the National Institutes of Health (1R35GM142760-01 to DHL and 1R01HL142587 to JMB). We thank Drs. Megan Bergkessel (University of Dundee), Melanie Spero (University of Oregon), Alex Horswill (University of Colorado Denver), Mike Schurr (University of Colorado Denver), and Li Wu (University of Iowa) for helpful discussions and valuable insight. We also thank members of the Limoli and Tirrell Labs for careful editing of the manuscript and helpful discussions. We thank Dr. Jeff Jones (Caltech) for an in-house pipeline for proteomics data processing, Dr. J. Muse Davis for the use of the stereoscope, and Drs. Joseph Mougous and Anupama Khare for the generous gifts of the ClpV1-GFPmut3 and P'pvdA-mScarlet reporters, respectively. \n\nThe authors have declared no competing interest.\n\nSubmitted - 2023.01.29.526047v1.full.pdf
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", "abstract": "Coinfection with two notorious opportunistic pathogens, the Gram-negative Pseudomonas aeruginosa and Gram-positiveStaphylococcus aureus, dominates chronic pulmonary infections. While coinfection is associated with poor patient outcomes, the interspecies interactions responsible for such decline remain unknown. Here, we dissected molecular mechanisms of interspecies sensing between P. aeruginosa and S. aureus. We discovered that P. aeruginosa senses S. aureus secreted peptides and, counterintuitively, moves towards these toxins. P. aeruginosa tolerates such a strategy through \"competition sensing\", whereby it preempts imminent danger/competition by arming cells with type six secretion (T6S) and iron acquisition systems. Intriguingly, while T6S is predominantly described as weaponry targeting Gram-negative and eukaryotic cells, we find that T6S is essential for full P. aeruginosa competition with S. aureus, a previously undescribed role for T6S. Importantly, competition sensing was activated during coinfection of bronchial epithelia, including T6S islands targeting human cells. This study reveals critical insight into both interspecies competition and how antagonism may cause collateral damage to the host environment.", "date": "2023-03-21", "date_type": "published", "id_number": "CaltechAUTHORS:20230316-182348000.27", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20230316-182348000.27", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Jacobs Institute for Molecular Engineering for Medicine" }, { "agency": "Caltech Center for Environmental Microbial Interactions (CEMI)" }, { "agency": "Army Research Office (ARO)", "grant_number": "W911NF-19-2-0026" }, { "agency": "Cystic Fibrosis Foundation", "grant_number": "LIMOLI19R3" }, { "agency": "Cystic Fibrosis Foundation", "grant_number": "BOMBER18G0" }, { "agency": "NIH", "grant_number": "1R35GM142760-01" }, { "agency": "NIH", "grant_number": "1R01HL142587" } ] }, "local_group": { "items": [ { "id": "Jacobs-Institute-for-Molecular-Engineering-for-Medicine" }, { "id": "Caltech-Center-for-Environmental-Microbial-Interactions-(CEMI)" }, { "id": "Division-of-Biology-and-Biological-Engineering" } ] }, "doi": "10.1101/2023.01.29.526047", "primary_object": { "basename": "2023.01.29.526047v1.full.pdf", "url": "https://authors.library.caltech.edu/records/vv73j-vph14/files/2023.01.29.526047v1.full.pdf" }, "related_objects": [ { "basename": "media-1.pdf", "url": "https://authors.library.caltech.edu/records/vv73j-vph14/files/media-1.pdf" }, { "basename": "media-2.xlsx", "url": "https://authors.library.caltech.edu/records/vv73j-vph14/files/media-2.xlsx" }, { "basename": "media-3.xlsx", "url": "https://authors.library.caltech.edu/records/vv73j-vph14/files/media-3.xlsx" }, { "basename": "media-4.xlsx", "url": "https://authors.library.caltech.edu/records/vv73j-vph14/files/media-4.xlsx" } ], "resource_type": "monograph", "pub_year": "2023", "author_list": "Wang, Grace Z.; Warren, Elizabeth A.; et el." }, { "id": "https://authors.library.caltech.edu/records/cdpes-fvh20", "eprint_id": 120177, "eprint_status": "archive", "datestamp": "2023-08-20 08:47:42", "lastmod": "2023-12-13 16:47:53", "type": "monograph", "metadata_visibility": "show", "creators": { "items": [ { "id": "Findlay-Andrew-R", "name": { "family": "Findlay", "given": "Andrew R." }, "orcid": "0000-0002-8728-9833" }, { "id": "Paing-May-M", "name": { "family": "Paing", "given": "May M." } }, { "id": "Daw-Jil-A", "name": { "family": "Daw", "given": "Jil A." }, "orcid": "0000-0002-8002-076X" }, { "id": "Bengoechea-Ibaceta-Rocio", "name": { "family": "Bengoechea", "given": "Rocio" }, "orcid": "0000-0002-9029-019X" }, { "id": "Pittman-Sara-K", "name": { "family": "Pittman", "given": "Sara K." } }, { "id": "Li-Shan", "name": { "family": "Li", "given": "Shan" }, "orcid": "0000-0002-0829-1821" }, { "id": "Wang-Feng", "name": { "family": "Wang", "given": "Feng" }, "orcid": "0000-0003-4742-2668" }, { "id": "Miller-Timothy-M", "name": { "family": "Miller", "given": "Timothy M." }, "orcid": "0000-0002-3424-5511" }, { "id": "True-Heather-L", "name": { "family": "True", "given": "Heather L." }, "orcid": "0000-0003-4824-9529" }, { "id": "Chou-Tsui-Fen", "name": { "family": "Chou", "given": "Tsui-Fen" }, "orcid": "0000-0003-2410-2186" }, { "id": "Weihl-Conrad-C", "name": { "family": "Weihl", "given": "Conrad C." }, "orcid": "0000-0002-3816-6124" } ] }, "title": "DNAJB6 Isoform Specific Knockdown: Therapeutic Potential for LGMDD1", "ispublished": "unpub", "full_text_status": "public", "note": "The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. \n\nThis work was supported by grants from: The National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS): ARF (K08AR075894, R03AR081395), CCW (R01AR068797, K24AR073317); The American Society of Gene and Cell therapy (ASGCT): ARF (Career Development Award); The Children's Discovery Institute of Saint Louis Children's Hospital: ARF (Faculty Scholar Award- MIFR20221004); and the LGMD-1D DNAJB6 Foundation and International Registry (ARF). \n\nAuthor Contributions: \nARF: Conceptualization, formal analysis, funding acquisition, investigation, methodology, resources, supervision, validation, visualization, writing original draft, writing \u2013 review and editing. \nMMP, JAD, RB, SKP, SL, FW, TC: Investigation, methodology. \nHLT, TMM: Conceptualization, writing \u2013 review and editing. \nCCW: Conceptualization, funding acquisition, resources, supervision, validation, writing \u2013 review and editing. \n\nCompeting Interest Statement. ARF and CCW are co-inventors on a pending patent application related to this publication (USPTO serial no. 17/932,996).\n\nSubmitted - 2022.11.17.516920v1.full.pdf
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", "abstract": "Dominant missense mutations in DNAJB6, an HSP40 co-chaperone, cause limb girdle muscular dystrophy (LGMD) D1. No treatments are currently available. Two isoforms exist, DNAJB6a and DNAJB6b, each with distinct localizations in muscle. Mutations reside in both isoforms, yet evidence suggests only DNAJB6b is responsible for disease pathogenesis. Mechanistic data supports either a toxic gain of function, a dominant negative mechanism, or a combination of both. Knockdown treatment strategies involving both isoforms carry risk as DNAJB6 knockout is embryonic lethal. We therefore developed an isoform specific knockdown approach using morpholinos. Selective reduction of each isoform was achievedin-vitroin primary mouse myotubes and human myoblasts, as well asin-vivoin mouse skeletal muscle. To assess isoform specific knockdown in LGMDD1, we created primary myotube cultures from aknock-inLGMDD1 mouse model. Using mass spectrometry, we identified an LGMDD1 protein signature related to protein homeostasis and myofibril structure. Selective reduction of DNAJB6b levels in LGMDD1 myotubes corrected much of the proteomic disease signature towards wild type levels. While additionalin-vivofunctional data is required, these findings suggest selective reduction of DNAJB6b may be a viable therapeutic target for LGMDD1.", "date": "2023-03-17", "date_type": "published", "id_number": "CaltechAUTHORS:20230316-182861000.70", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20230316-182861000.70", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "K08AR075894" }, { "agency": "NIH", "grant_number": "R03AR081395" }, { "agency": "NIH", "grant_number": "R01AR068797" }, { "agency": "NIH", "grant_number": "K24AR073317" }, { "agency": "American Society of Gene and Cell Therapy" }, { "agency": "Saint Louis Children's Hospital", "grant_number": "MIFR20221004" }, { "agency": "LGMD-1D DNAJB6 Foundation" } ] }, "local_group": { "items": [ { "id": "Division-of-Biology-and-Biological-Engineering" } ] }, "doi": "10.1101/2022.11.17.516920", "primary_object": { "basename": "2022.11.17.516920v1.full.pdf", "url": "https://authors.library.caltech.edu/records/cdpes-fvh20/files/2022.11.17.516920v1.full.pdf" }, "related_objects": [ { "basename": "media-1.xlsx", "url": "https://authors.library.caltech.edu/records/cdpes-fvh20/files/media-1.xlsx" } ], "resource_type": "monograph", "pub_year": "2023", "author_list": "Findlay, Andrew R.; Paing, May M.; et el." }, { "id": "https://authors.library.caltech.edu/records/82fne-ypv78", "eprint_id": 119571, "eprint_status": "archive", "datestamp": "2023-08-20 08:34:01", "lastmod": "2023-12-22 23:35:10", "type": "monograph", "metadata_visibility": "show", "creators": { "items": [ { "id": "Guna-Alina", "name": { "family": "Guna", "given": "Alina" }, "orcid": "0000-0003-0757-1255" }, { "id": "Stevens-Taylor-A", "name": { "family": "Stevens", "given": "Taylor A." }, "orcid": "0000-0002-6232-5316" }, { "id": "Inglis-Alison-J", "name": { "family": "Inglis", "given": "Alison J." }, "orcid": "0000-0002-9008-8565" }, { "id": "Replogle-Joseph-M", "name": { "family": "Replogle", "given": "Joseph M." }, "orcid": "0000-0003-1832-919X" }, { "id": "Esantsi-Theodore-K", "name": { "family": "Esantsi", "given": "Theodore K." } }, { "id": "Muthukumar-Gayathri", "name": { "family": "Muthukumar", "given": "Gayathri" } }, { "id": "Shaffer-Kelly-C-L", "name": { "family": "Shaffer", "given": "Kelly C.L." }, "orcid": "0000-0002-6212-1428" }, { "id": "Wang-Maxine-L", "name": { "family": "Wang", "given": "Maxine L." }, "orcid": "0000-0002-5285-1857" }, { "id": "Pogson-Angela-N", "name": { "family": "Pogson", "given": "Angela N." }, "orcid": "0000-0002-6927-2456" }, { "id": "Jones-Jeffrey-J", "name": { "family": "Jones", "given": "Jeff J." }, "orcid": "0000-0002-7142-2222" }, { "id": "Lomenick-Brett", "name": { "family": "Lomenick", "given": "Brett" }, "orcid": "0000-0002-5023-9998" }, { "id": "Chou-Tsui-Fen", "name": { "family": "Chou", "given": "Tsui-Fen" }, "orcid": "0000-0003-2410-2186" }, { "id": "Weissman-Jonathan-S", "name": { "family": "Weissman", "given": "Jonathan S." }, "orcid": "0000-0003-2445-670X" }, { "id": "Voorhees-R-M", "name": { "family": "Voorhees", "given": "Rebecca M." }, "orcid": "0000-0003-1640-2293" } ] }, "title": "MTCH2 is a mitochondrial outer membrane protein insertase", "ispublished": "unpub", "full_text_status": "public", "note": "The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. \n\nWe thank T. Pleiner and Z. Levine for careful reading and input on the manuscript. We thank: the Whitehead Institute Flow Cytometry Core and Kathy Daniels for access to FACS machines; the Whitehead Institute Genome Technology Core for support with sequencing of screen libraries; the Caltech Flow cytometry facility; and the Ting-Yu Wang and the Proteome Exploration Laboratory at Caltech for support for mass spectrometry. \n\nResearch reported in this publication was supported by: Howard Hughes Medical Institute (JSW), Human Frontier Science Program 2019L/LT000858 (AG), the Heritage Medical Research Institute (RMV), and the Larry L. Hillblom Foundation (AJI). \n\nCompeting Interest Statement. JMR consults for Maze Therapeutics and is a consultant for and equity holder in Waypoint Bio. JSW declares outside interest in 5 AM Venture, Amgen, Chroma Medicine, KSQ Therapeutics, Maze Therapeutics, Tenaya Therapeutics, Tessera Therapeutics and Third Rock Ventures. RMV is a consultant and equity holder in Gate Bioscience.\n\nSubmitted - 2022.09.15.508165v1.full.pdf
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", "abstract": "In the mitochondrial outer membrane, tail-anchored (TA) proteins play critical roles in cytoplasmic-mitochondrial communication. Using genome-wide CRISPRi screens, we identify factors involved in mitochondrial TA biogenesis in human cells. We show that MTCH2, and its paralog MTCH1, are required for insertion of biophysically diverse mitochondrial TAs, but not outer membrane \u03b2-barrel proteins. In a reconstituted system, purified MTCH2 is sufficient to mediate insertion into proteoliposomes. Functional and mutational studies reveal that MTCH2 uses membrane-embedded hydrophilic residues to function as a gatekeeper for outer membrane protein biogenesis, controlling mislocalization of TAs into the endoplasmic reticulum and the sensitivity of leukemia cells to apoptosis. Our identification of MTCH2 as an insertase provides a mechanistic explanation for the diverse phenotypes and disease states associated with MTCH2 dysfunction.One-Sentence SummaryMTCH2 is both necessary and sufficient for insertion of diverse \u03b1-helical proteins into the mitochondrial outer membrane, and is the defining member of a family of insertases that have co-opted the SLC25 transporter fold.", "date": "2023-02-28", "date_type": "published", "id_number": "CaltechAUTHORS:20230228-37943000.2", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20230228-37943000.2", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Howard Hughes Medical Institute (HHMI)" }, { "agency": "Human Frontier Science Program", "grant_number": "2019L/LT000858" }, { "agency": "Heritage Medical Research Institute" }, { "agency": "Larry L. Hillblom Foundation" } ] }, "local_group": { "items": [ { "id": "Heritage-Medical-Research-Institute" }, { "id": "Tianqiao-and-Chrissy-Chen-Institute-for-Neuroscience" }, { "id": "Division-of-Biology-and-Biological-Engineering" } ] }, "doi": "10.1101/2022.09.15.508165", "primary_object": { "basename": "2022.09.15.508165v1.full.pdf", "url": "https://authors.library.caltech.edu/records/82fne-ypv78/files/2022.09.15.508165v1.full.pdf" }, "related_objects": [ { "basename": "media-1.pdf", "url": "https://authors.library.caltech.edu/records/82fne-ypv78/files/media-1.pdf" }, { "basename": "media-2.xlsx", "url": "https://authors.library.caltech.edu/records/82fne-ypv78/files/media-2.xlsx" }, { "basename": "media-3.xlsx", "url": "https://authors.library.caltech.edu/records/82fne-ypv78/files/media-3.xlsx" }, { "basename": "media-4.xlsx", "url": "https://authors.library.caltech.edu/records/82fne-ypv78/files/media-4.xlsx" } ], "resource_type": "monograph", "pub_year": "2023", "author_list": "Guna, Alina; Stevens, Taylor A.; et el." }, { "id": "https://authors.library.caltech.edu/records/yvx4e-r7d09", "eprint_id": 115351, "eprint_status": "archive", "datestamp": "2023-08-20 08:02:20", "lastmod": "2023-12-22 23:34:59", "type": "monograph", "metadata_visibility": "show", "creators": { "items": [ { "id": "Dutka-Przemys\u0142aw", "name": { "family": "Dutka", "given": "Przemys\u0142aw" }, "orcid": "0000-0003-3819-1618" }, { "id": "Metskas-Lauren-Ann", "name": { "family": "Metskas", "given": "Lauren Ann" }, "orcid": "0000-0002-8073-6960" }, { "id": "Hurt-Robert-C", "name": { "family": "Hurt", "given": "Robert C." }, "orcid": "0000-0002-4347-6901" }, { "id": "Salahshoor-Hossein", "name": { "family": "Salahshoor", "given": "Hossein" }, "orcid": "0000-0002-7264-7650" }, { "id": "Wang-Ting-Yu", "name": { "family": "Wang", "given": "Ting-Yu" } }, { "id": "Malounda-Dina", "name": { "family": "Malounda", "given": "Dina" }, "orcid": "0000-0001-7086-9877" }, { "id": "Lu-George-Jiaozhi", "name": { "family": "Lu", "given": "George" }, "orcid": "0000-0002-4689-9686" }, { "id": "Chou-Tsui-Fen", "name": { "family": "Chou", "given": "Tsui-Fen" }, "orcid": "0000-0003-2410-2186" }, { "id": "Shapiro-M-G", "name": { "family": "Shapiro", "given": "Mikhail G." }, "orcid": "0000-0002-0291-4215" }, { "id": "Jensen-G-J", "name": { "family": "Jensen", "given": "Grant J." }, "orcid": "0000-0003-1556-4864" } ] }, "title": "Structure of Anabaena flos-aquae gas vesicles revealed by cryo-ET", "ispublished": "unpub", "full_text_status": "public", "note": "The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. \n\nVersion 1 June 21, 2022; Version 2 - July 12, 2022. \n\nThe authors are grateful to Catherine Oikonomou for helpful editorial comments. We thank Songye Chen for assistance with tomography data collection. Electron microscopy was performed in the Beckman Institute Resource Center for Transmission Electron Microscopy at Caltech. The Proteome Exploration Laboratory (PEL) is supported by the Beckman Institute and NIH 1S10OD02001301. This work was supported by the National Institutes of Health (grant R01-AI127401 to G.J.J. and R01-EB018975 to M.G.S.) and the Caltech Center for Environmental Microbial Interactions (CEMI). Related research in the Shapiro Laboratory is supported by the Packard Foundation, the Chan Zuckerberg Initiative and the Heritage Medical Research Institute. \n\nAuthor Contributions: P.D. conceived experiments, prepared samples, acquired and analyzed data, performed data exploration, drafted the manuscript, and prepared the figures. L.A.M initiated the project and collected data for Mega GVs. R.C.H performed mutation screening for GvpA and participated in initial sample preparation and optimization for Mega GVs. H.S. performed finite element simulation and analyzed data. T-Y.W performed XLMS experiments and analyzed the data. D.M expressed and purified GV samples. G.L. participated in initial sample preparation and optimization for Mega GVs. T-F.C. supervised XLMS experiments. All authors participated in correction of the manuscript. M.G.S. participated in guidance, experimental design, funding, and correction/advising on writing the manuscript. G.J.J participated in guidance, experimental design, funding, and correction/advising on writing the manuscript. \n\nThe authors declare no competing interests. \n\nData Availability: Cryo-ET density maps and GvpA/GvpC integrative model are available on Zenodo zenodo.org/record/6820642#.Ys0aROzMKw1\n\nSubmitted - 2022.06.21.496981v2.full.pdf
Supplemental Material - media-1.avi
", "abstract": "Gas vesicles (GVs) are gas-filled protein nanostructures employed by several species of bacteria and archaea as flotation devices to enable access to optimal light and nutrients. The unique physical properties of GVs have led to their use as genetically-encodable contrast agents for ultrasound and MRI. Currently, however, the structure and assembly mechanism of GVs remain unknown. Here we employ cryo-electron tomography to reveal how the GV shell is formed by a helical filament of highly conserved GvpA subunits. This filament changes polarity at the center of the GV cylinder\u2014a site that may act as an elongation center. High-resolution subtomogram averaging reveals a corrugated pattern of the shell arising from polymerization of GvpA into a \u03b2-sheet. The accessory protein GvpC forms a helical cage around the GvpA shell, providing structural reinforcement. Together, our results help explain the remarkable mechanical properties of GVs and their ability to adopt different diameters and shapes.", "date": "2022-07-08", "date_type": "published", "id_number": "CaltechAUTHORS:20220706-965078000", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20220706-965078000", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Caltech Beckman Institute" }, { "agency": "NIH", "grant_number": "1S10OD02001301" }, { "agency": "NIH", "grant_number": "R01-AI127401" }, { "agency": "NIH", "grant_number": "R01-EB018975" }, { "agency": "Caltech Center for Environmental Microbial Interactions (CEMI)" }, { "agency": "David and Lucile Packard Foundation" }, { "agency": "Chan Zuckerberg Initiative" }, { "agency": "Heritage Medical Research Institute" } ] }, "local_group": { "items": [ { "id": "Caltech-Center-for-Environmental-Microbial-Interactions-(CEMI)" }, { "id": "Heritage-Medical-Research-Institute" }, { "id": "Division-of-Biology-and-Biological-Engineering" } ] }, "doi": "10.1101/2022.06.21.496981", "primary_object": { "basename": "2022.06.21.496981v2.full.pdf", "url": "https://authors.library.caltech.edu/records/yvx4e-r7d09/files/2022.06.21.496981v2.full.pdf" }, "related_objects": [ { "basename": "media-1.avi", "url": "https://authors.library.caltech.edu/records/yvx4e-r7d09/files/media-1.avi" } ], "resource_type": "monograph", "pub_year": "2022", "author_list": "Dutka, Przemys\u0142aw; Metskas, Lauren Ann; et el." }, { "id": "https://authors.library.caltech.edu/records/wd2ea-4j472", "eprint_id": 110190, "eprint_status": "archive", "datestamp": "2023-08-20 04:40:20", "lastmod": "2023-12-22 23:24:06", "type": "monograph", "metadata_visibility": "show", "creators": { "items": [ { "id": "Le-Steven-Q", "name": { "family": "Le", "given": "Steven Q." } }, { "id": "Kan-Shih-hsin", "name": { "family": "Kan", "given": "Shih-hsin" } }, { "id": "Nu\u00f1ez-Marie", "name": { "family": "Nu\u00f1ez", "given": "Marie" } }, { "id": "Dearborn-Joshua-T", "name": { "family": "Dearborn", "given": "Joshua T." }, "orcid": "0000-0003-0335-1087" }, { "id": "Wang-Feng", "name": { "family": "Wang", "given": "Feng" } }, { "id": "Li-Shan", "name": { "family": "Li", "given": "Shan" }, "orcid": "0000-0002-0829-1821" }, { "id": "Snella-Elizabeth-M", "name": { "family": "Snella", "given": "Liz" }, "orcid": "0000-0003-1482-2876" }, { "id": "Jens-Jackie-K", "name": { "family": "Jens", "given": "Jackie K." } }, { "id": "Valentine-Bethann-N", "name": { "family": "Valentine", "given": "Bethann N." } }, { "id": "Nelvagal-Hemanth-R", "name": { "family": "Nelvagal", "given": "Hemanth R." }, "orcid": "0000-0003-2407-4517" }, { "id": "Sorensen-Alexander", "name": { "family": "Sorensen", "given": "Alexander" } }, { "id": "Cooper-Jonathan-D", "name": { "family": "Cooper", "given": "Jonathan D." }, "orcid": "0000-0003-1339-4750" }, { "id": "Chou-Tsui-Fen", "name": { "family": "Chou", "given": "Tsui-Fen" }, "orcid": "0000-0003-2410-2186" }, { "id": "Ellinwood-N-Matthew", "name": { "family": "Ellinwood", "given": "N. Matthew" }, "orcid": "0000-0002-1701-5052" }, { "id": "Smith-Jodi-D", "name": { "family": "Smith", "given": "Jodi D." }, "orcid": "0000-0001-7952-8024" }, { "id": "Sands-Mark-S", "name": { "family": "Sands", "given": "Mark S." }, "orcid": "0000-0002-5559-0832" }, { "id": "Dickson-Patricia-I", "name": { "family": "Dickson", "given": "Patricia I." } } ] }, "title": "Recombinant NAGLU-IGF2 prevents physical and neurological disease and improves survival in Sanfilippo B syndrome", "ispublished": "unpub", "full_text_status": "public", "keywords": "mucopolysaccharidosis, enzyme replacement therapy, glycosaminoglycan, proteomics, lysosomal storage disease", "note": "The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. \n\nVersion 1 - August 8, 2021; Version 2 - September 15, 2021; Version 3 - September 16, 2021. \n\nP.I.D., J.T.D., M.S.S., and J.D.C. designed experiments and prepared the manuscript. S.Q.L., S.-h.K., M.N., and J.T.D. performed mouse experiments. S.Q.L, A.S., H.R.N., and J.D.C. performed quantitative immunofluorescence. L.S., B.N.V., N.M.E., J.J., and J.D.S. performed canine experiments. F.W., S.L, S.Q.L., and T.F.C. performed enzyme assays and/or proteomics on canine tissues. We gratefully acknowledge the assistance and support of Soila Sukipolvi, Irina Zhuravka, George Lopez, Ling Wang, Valentina Sanguez, and Catalina Guerra. BioMarin Pharmaceutical provided vehicle, rhNAGLU, and rhNAGLU-IGF2. BioMarin provided HS measurement of mouse brain and heart tissues. We gratefully acknowledge Roger Lawrence and Brett Crawford for their specific assistance with these assays. \n\nResearch was supported by R01 NS088766 to P.I.D. The Washington University Animal Behavioral services are supported by the Eunice Kennedy Shriver National Institute Of Child Health & Human Development of the National Institutes of Health under Award Number P50 HD103525 to the Intellectual and Developmental Disabilities Research Center at Washington University. A traineeship from 5T32 GM8243-28 (to S.-h.K.) The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The UCLA Behavioral Testing Core is supported by the UCLA Bioscience Core Funding Initiative. Immunofluorescence imaging was performed in part through the use of Washington University Center for Cellular Imaging (WUCCI) supported by Washington University School of Medicine, The Children's Discovery Institute of Washington University and St. Louis Children's Hospital (CDI-CORE-2015-505 and CDI-CORE-2019-813) and the\nFoundation for Barnes-Jewish Hospital (3770 and 4642). \n\nConflicts of Interest: BioMarin Pharmaceutical Inc provided research materials for this study. Dr. Dickson receives research support from Genzyme and research materials from M6P Therapeutics.\n\nSubmitted - 2021.08.06.455469v3.full.pdf
Supplemental Material - media-1.docx
Supplemental Material - media-2.xlsx
", "abstract": "Recombinant human alpha-N-acetylglucosaminidase-insulin-like growth factor-2 (rhNAGLU-IGF2) is an investigational enzyme replacement therapy for Sanfilippo B, a lysosomal storage disease. Because recombinant human NAGLU (rhNAGLU) is poorly mannose 6-phosphorylated, we generated a fusion protein of NAGLU with IGF2 to permit its binding to the cation-independent mannose 6-phosphate receptor. We previously administered rhNAGLU-IGF2 intracerebroventricularly to Sanfilippo B mice, and demonstrated therapeutic restoration of NAGLU, normalization of lysosomal storage, and improvement in markers of neurodegeneration and inflammation. Here, we studied intracerebroventricular rhNAGLU-IGF2 delivery in both murine and canine Sanfilippo B to determine potential effects on their behavioral phenotypes and survival. Treated mice showed improvement in disease markers such as heparan sulfate glycosaminoglycans, beta-hexosaminidase, microglial activation, and lysosomal-associated membrane protein-1. Sanfilippo B mice treated with rhNAGLU-IGF2 displayed partial normalization of their stretch attend postures, a defined fear pose in mice (p<0.001). We found a more normal dark/light activity pattern in Sanfilippo B mice treated with rhNAGLU-IGF2 compared to vehicle-treated Sanfilippo B mice (p=0.025). We also found a 61% increase in survival in Sanfilippo B mice treated with rhNAGLU-IGF2 (mean 53w, median 48w) compared to vehicle-treated Sanfilippo B mice (mean 33w, median 37w; p<0.001). In canine Sanfilippo B, we found that rhNAGLU-IGF2 administered into cerebrospinal fluid normalized HS and beta-hexosaminidase activity in gray and white matter brain regions. Proteomic analysis of cerebral cortex showed restoration of protein expression levels in pathways relevant to cognitive function, synapse, and the lysosome. These data suggest that treatment with rhNAGLU-IGF2 may improve the phenotype of Sanfilippo B disease.", "date": "2021-08-11", "date_type": "published", "id_number": "CaltechAUTHORS:20210810-163528980", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20210810-163528980", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "R01 NS088766" }, { "agency": "NIH", "grant_number": "P50 HD103525" }, { "agency": "NIH Predoctoral Fellowship", "grant_number": "5T32 GM8243-28" }, { "agency": "UCLA" }, { "agency": "Washington University" }, { "agency": "Children's Discovery Institute" }, { "agency": "St. Louis Children's Hospital Foundation", "grant_number": "CDI-CORE-2015-505" }, { "agency": "St. Louis Children's Hospital Foundation", "grant_number": "CDI-CORE-2019-813" }, { "agency": "Foundation for Barnes-Jewish Hospital", "grant_number": "3770" }, { "agency": "Foundation for Barnes-Jewish Hospital", "grant_number": "4642" } ] }, "local_group": { "items": [ { "id": "Division-of-Biology-and-Biological-Engineering" } ] }, "doi": "10.1101/2021.08.06.455469", "primary_object": { "basename": "media-2.xlsx", "url": "https://authors.library.caltech.edu/records/wd2ea-4j472/files/media-2.xlsx" }, "related_objects": [ { "basename": "2021.08.06.455469v3.full.pdf", "url": "https://authors.library.caltech.edu/records/wd2ea-4j472/files/2021.08.06.455469v3.full.pdf" }, { "basename": "media-1.docx", "url": "https://authors.library.caltech.edu/records/wd2ea-4j472/files/media-1.docx" } ], "resource_type": "monograph", "pub_year": "2021", "author_list": "Le, Steven Q.; Kan, Shih-hsin; et el." }, { "id": "https://authors.library.caltech.edu/records/vyzbv-daf40", "eprint_id": 106783, "eprint_status": "archive", "datestamp": "2023-08-20 00:25:24", "lastmod": "2023-12-13 16:46:45", "type": "monograph", "metadata_visibility": "show", "creators": { "items": [ { "id": "Arango-Gonzalez-Bianca", "name": { "family": "Arango-Gonzalez", "given": "Blanca" }, "orcid": "0000-0002-9045-182X" }, { "id": "Sen-Merve", "name": { "family": "Sen", "given": "Merve" } }, { "id": "Guarascio-Rosellina", "name": { "family": "Guarascio", "given": "Rosellina" } }, { "id": "Ziaka-Kalliopi", "name": { "family": "Ziaka", "given": "Kalliopi" } }, { "id": "del-Amo-E-M", "name": { "family": "del Amo", "given": "Eva M." }, "orcid": "0000-0002-5705-4515" }, { "id": "Hau-Kwan", "name": { "family": "Hau", "given": "Kwan" } }, { "id": "Poultney-Hannah", "name": { "family": "Poultney", "given": "Hannah" } }, { "id": "Asfahani-Rowan", "name": { "family": "Asfahani", "given": "Rowan" } }, { "id": "Urtti-Arto", "name": { "family": "Urtti", "given": "Arto" }, "orcid": "0000-0001-6064-3102" }, { "id": "Chou-Tsui-Fen", "name": { "family": "Chou", "given": "Tsui-Fen" }, "orcid": "0000-0003-2410-2186" }, { "id": "Bolz-Sylvia", "name": { "family": "Bolz", "given": "Sylvia" } }, { "id": "Deshaies-R-J", "name": { "family": "Deshaies", "given": "Raymond J." }, "orcid": "0000-0002-3671-9354" }, { "id": "Haq-Wadood", "name": { "family": "Haq", "given": "Wadood" } }, { "id": "Cheetham-M-E", "name": { "family": "Cheetham", "given": "Michael E." }, "orcid": "0000-0001-6429-654X" }, { "id": "Ueffing-Marius", "name": { "family": "Ueffing", "given": "Marius" }, "orcid": "0000-0003-2209-2113" } ] }, "title": "Inhibition of VCP preserves retinal structure and function in autosomal dominant retinal degeneration", "ispublished": "unpub", "full_text_status": "public", "note": "The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. \n\nThis version posted November 19, 2020. \n\nThis study was supported by funds (to M.Ue. and B.A-G) from FFB (Grant PPA-0717-0719-RAD), Kerstan Foundation, European Union's Horizon 2020 research and innovation programme under the Marie Sk\u0142odowska-Curie (Grant agreement No. 722717 \u2013 project OCUTHER) and ProRetina Foundation. The personnel of the animal husbandry at the Universit\u00e4tsklinikums T\u00fcbingen and Norman Rieger are acknowledged for the animal care. Christine Henes is acknowledged for her skilled technical assistance with the experiments. Ellen Kilger and Sally Williamson are gratefully acknowledged for language editing and proofreading. \n\nAuthors contributions: B.A.-G. designed experiments, carried out and treated organotypic cultures, performed intravitreal injections, prepared, stained, and imaged histological samples, analyzed the experimental data, and wrote the manuscript. M.S. carried out and treated organotypic cultures, prepared, stained, and imaged histological samples. M.S. and W.H. planned and carried out the ex-vivo light stimulation and activity recordings of the retinal explants. M.S. and E.M.A. performed the in silico calculations. R.G., K.H, K.Z., H.P., R.A., and. M.C. performed intravitreal injections and corresponding ERG and contributed to study planning therein. S.B. performed the EM and prepared histological samples. T.-F.C., R.D., A.U. participated in planning the study, and M.Ue. designed and coordinated the project, participated in designing the experiments, wrote the manuscript, and acquired funding for the studies. All authors have provided feedback on the results, read and approved the final manuscript.\nB.A.-G. and M.S. are co-first authors. B.A.-G. is listed first because she contributed more to the conception of the project and the writing of the manuscript.\n\nSubmitted - 2020.11.17.384669v1.full.pdf
Supplemental Material - media-1.docx
Supplemental Material - media-2.docx
Supplemental Material - media-3.docx
Supplemental Material - media-4.docx
Supplemental Material - media-5.docx
", "abstract": "Due to continuously high production rates of rhodopsin (RHO) and high metabolic activity, photoreceptor neurons are especially vulnerable to defects in proteostasis. A proline to histidine substitution at position 23 (P23H) leads to production of structurally misfolded RHO, causing the most common form of autosomal dominant Retinitis Pigmentosa (adRP) in North America. The AAA-ATPase valosin-containing protein (VCP) extracts misfolded proteins from the ER membrane for cytosolic degradation. Here, we provide the first evidence that inhibition of VCP activity rescues degenerating P23H rod cells and improves their functional properties in P23H transgenic rat and P23H knock-in mouse retinae, both in vitro and in vivo. This improvement correlates with the restoration of the physiological RHO localization to rod outer segments (OS) and properly-assembled OS disks. As a single intravitreal injection suffices to deliver a long-lasting benefit in vivo, we suggest VCP inhibition as a potential therapeutic strategy for adRP patients carrying mutations in the RHO gene.", "date": "2020-11-23", "date_type": "published", "id_number": "CaltechAUTHORS:20201123-120919400", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20201123-120919400", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Foundation Fighting Blindness", "grant_number": "PPA-0717-0719-RAD" }, { "agency": "Kerstan Foundation" }, { "agency": "Marie Curie Fellowship", "grant_number": "722717" }, { "agency": "ProRetina Foundation" } ] }, "local_group": { "items": [ { "id": "Division-of-Biology-and-Biological-Engineering" } ] }, "doi": "10.1101/2020.11.17.384669", "primary_object": { "basename": "media-2.docx", "url": "https://authors.library.caltech.edu/records/vyzbv-daf40/files/media-2.docx" }, "related_objects": [ { "basename": "media-3.docx", "url": "https://authors.library.caltech.edu/records/vyzbv-daf40/files/media-3.docx" }, { "basename": "media-4.docx", "url": "https://authors.library.caltech.edu/records/vyzbv-daf40/files/media-4.docx" }, { "basename": "media-5.docx", "url": "https://authors.library.caltech.edu/records/vyzbv-daf40/files/media-5.docx" }, { "basename": "2020.11.17.384669v1.full.pdf", "url": "https://authors.library.caltech.edu/records/vyzbv-daf40/files/2020.11.17.384669v1.full.pdf" }, { "basename": "media-1.docx", "url": "https://authors.library.caltech.edu/records/vyzbv-daf40/files/media-1.docx" } ], "resource_type": "monograph", "pub_year": "2020", "author_list": "Arango-Gonzalez, Blanca; Sen, Merve; et el." } ]