[ { "id": "https://authors.library.caltech.edu/records/gpt4a-fka26", "eprint_id": 120341, "eprint_status": "archive", "datestamp": "2023-08-20 08:31:20", "lastmod": "2023-12-13 17:24:23", "type": "monograph", "metadata_visibility": "show", "creators": { "items": [ { "id": "Lee-Peter-H", "name": { "family": "Lee", "given": "Peter H." }, "orcid": "0000-0003-2411-6094" }, { "id": "Anaya-Michael-A", "name": { "family": "Anaya", "given": "Michael" }, "orcid": "0000-0002-6944-3614" }, { "id": "Ladinsky-Mark-S", "name": { "family": "Ladinsky", "given": "Mark S." }, "orcid": "0000-0002-1036-3513" }, { "id": "Reitsma-Justin-M", "name": { "family": "Reitsma", "given": "Justin M." }, "orcid": "0000-0002-2700-6440" }, { "id": "Zinn-K", "name": { "family": "Zinn", "given": "Kai" }, "orcid": "0000-0002-6706-5605" } ] }, "title": "An extracellular vesicle targeting ligand that binds to Arc proteins and facilitates Arc transport in vivo", "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 4.0 International license. \n\nMass spectrometry work was performed at the Caltech Proteome Exploration Laboratory. Imaging was done at the Caltech Biological Imaging facility. EM work was done at the Caltech Cryo-EM facility. We thank Andre Malyutin for negative stain EM. We thank Violana Nesterova for figure preparation. We thank the following colleagues for reagents and Drosophila lines: Jason Shepherd (University of Utah) for pGEX-dArc and rArc constructs; Travis Thomson and Vivian Budnik (University of Massachusetts) for rabbit anti-Arc1; Douglas Cavener (Penn State) for rabbit anti-SasFL; Deborah Andrew (Johns Hopkins) for Sage-GAL4; James Skeath (Washington University) for guinea pig anti-Numb; Swati Banerjee (UTHSC, San Antonio) for rat anti-Repo, and Yuh-Nung Jan (UCSF) for UAS-Numb. We thank Simon Erlendsson, Fernando Bazan, Paul Worley, and Tino Pleiner for discussions about Arc purification and Arc and Sas structures. This work was supported by NIH RO1 grants NS28182 and NS096509 to K.Z., and by Howard Hughes Medical Institute support to R. Deshaies, who was J.M.R.'s faculty supervisor when he was a postdoctoral fellow at Caltech. \n\nAuthor Contributions. P. H. L. designed and performed the majority of the experiments. M.A. helped with protein biochemistry work. M.S.L. performed the immuno-EM and EM tomography experiments. J.M.R. performed the mass spectrometry analysis of V5 IPs from EVs. P. H. L. and K.Z. wrote the manuscript. K.Z. directed the project. \n\nCompeting Interest Statement. Justin M. Reitsma is affiliated with AbbVie. The author has no other competing interests to declare.\n\n
Submitted - 2022.09.06.506798v1.full.pdf
", "abstract": "Communication between distant cells can be mediated by extracellular vesicles (EVs) that deliver proteins and RNAs to recipient cells. Little is known about how EVs are targeted to specific cell types. Here we identify the Drosophila cell-surface protein Stranded at second (Sas) as a targeting ligand for EVs. Full-length Sas is present in EV preparations from transfected Drosophila Schneider 2 (S2 cells). Sas is a binding partner for the Ptp10D receptor tyrosine phosphatase, and Sas-bearing EVs preferentially target to cells expressing Ptp10D. We used co-immunoprecipitation and peptide binding to show that the cytoplasmic domain (ICD) of Sas binds to dArc1. dArc1 and mammalian Arc are related to retrotransposon Gag proteins. They form virus-like capsids which encapsulate Arc and other mRNAs and are transported between cells via EVs. The Sas ICD contains a motif required for dArc1 binding that is shared by the mammalian and Drosophila amyloid precursor protein (APP) orthologs, and the Sas and APP ICDs also bind to mammalian Arc. Sas facilitates delivery of dArc1 capsids bearing dArc1 mRNA into distant Ptp10D-expressing recipient cells in vivo.", "date": "2022-09-08", "date_type": "published", "id_number": "CaltechAUTHORS:20230322-367714000.27", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20230322-367714000.27", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "RO1 NS28182" }, { "agency": "NIH", "grant_number": "RO1 NS096509" }, { "agency": "Howard Hughes Medical Institute (HHMI)" } ] }, "local_group": { "items": [ { "id": "Division-of-Biology-and-Biological-Engineering" } ] }, "doi": "10.1101/2022.09.06.506798", "primary_object": { "basename": "2022.09.06.506798v1.full.pdf", "url": "https://authors.library.caltech.edu/records/gpt4a-fka26/files/2022.09.06.506798v1.full.pdf" }, "resource_type": "monograph", "pub_year": "2022", "author_list": "Lee, Peter H.; Anaya, Michael; et el." }, { "id": "https://authors.library.caltech.edu/records/k125e-vv934", "eprint_id": 115355, "eprint_status": "archive", "datestamp": "2023-08-20 08:03:06", "lastmod": "2023-12-13 17:24:43", "type": "monograph", "metadata_visibility": "show", "creators": { "items": [ { "id": "Siepe-Dirk-H", "name": { "family": "Siepe", "given": "Dirk H." }, "orcid": "0000-0002-0009-8023" }, { "id": "Henneberg-Lukas-T", "name": { "family": "Henneberg", "given": "Lukas T." }, "orcid": "0000-0003-3477-4541" }, { "id": "Wilson-Steven-C", "name": { "family": "Wilson", "given": "Steven C." } }, { "id": "Hess-Gaelen-T", "name": { "family": "Hess", "given": "Gaelen T." }, "orcid": "0000-0002-3836-0277" }, { "id": "Bassik-Michael-C", "name": { "family": "Bassik", "given": "Michael C." }, "orcid": "0000-0001-5185-8427" }, { "id": "Zinn-K", "name": { "family": "Zinn", "given": "Kai" }, "orcid": "0000-0002-6706-5605" }, { "id": "Garcia-K-Christopher", "name": { "family": "Garcia", "given": "K. Christopher" }, "orcid": "0000-0001-9273-0278" } ] }, "title": "Identification of orphan ligand-receptor relationships using a cell-based CRISPRa enrichment screening platform", "ispublished": "unpub", "full_text_status": "public", "keywords": "CRISPRa, pooled library, Cell-surface, protein-protein interaction, screen, receptor, ligand, protein communities, secreted proteome", "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\nThe authors thank the Howard Hughes Medical Institute (K.C.G.), and the G. Harold and Leila Y. Mathers Charitable Foundation (K.C.G.). \n\nAuthor Contributions Conceptualization, K.C.G., D.H.S.; Methodology, D.H.S., M.C.B. and K.G.G.; Library Design: D.H.S., K.Z., G.T.S., M.C.B. and K.C.G.; Screening, D.H.S., L.T.H.; Validation, D.H.S., S.C.W.; Analysis, D.H.S.; Investigation, D.H.S., L.T.H., and K.C.G.; Data Curation, D.H.S., K.Z.; Writing \u2013 Original Draft, D.H.S. and K.Z.; Writing \u2013 Review & Editing, K.C.G., D.H.S, and K.Z.; Visualization, D.H.S.; Supervision, K.C.G.; Funding Acquisition, K.C.G. \n\nThe authors have declared no competing interest.\n\nSubmitted - 2022.06.22.497261v2.full.pdf
", "abstract": "Secreted proteins, which include cytokines, hormones and growth factors, are extracellular ligands that control key signaling pathways mediating cell-cell communication within and between tissues and organs. Many drugs target secreted ligands and their cell-surface receptors. Still, there are hundreds of secreted human proteins that either have no identified receptors (\"orphans\") and are likely to act through cell surface receptors that have not yet been characterized. Discovery of secreted ligand-receptor interactions by high-throughput screening has been problematic, because the most commonly used high-throughput methods for protein-protein interaction (PPI) screening do not work well for extracellular interactions. Cell-based screening is a promising technology for definition of new ligand-receptor interactions, because multimerized ligands can enrich for cells expressing low affinity cell-surface receptors, and such methods do not require purification of receptor extracellular domains. Here, we present a proteo-genomic cell-based CRISPR activation (CRISPRa) enrichment screening platform employing customized pooled cell surface receptor sgRNA libraries in combination with a magnetic bead selection-based enrichment workflow for rapid, parallel ligand-receptor deorphanization. We curated 80 potentially high value orphan secreted proteins and ultimately screened 20 secreted ligands against two cell sgRNA libraries with targeted expression of all single-pass (TM1) or multi-pass (TM2+) receptors by CRISPRa. We identified previously unknown interactions in 12 of these screens, and validated several of them using surface plasmon resonance and/or cell binding. The newly deorphanized ligands include three receptor tyrosine phosphatase (RPTP) ligands and a chemokine like protein that binds to killer cell inhibitory receptors (KIR's). These new interactions provide a resource for future investigations of interactions between the human secreted and membrane proteomes.", "date": "2022-07-08", "date_type": "published", "id_number": "CaltechAUTHORS:20220706-965608000", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20220706-965608000", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "Howard Hughes Medical Institute (HHMI)" }, { "agency": "G. Harold and Leila Y. Mathers Charitable Foundation" } ] }, "local_group": { "items": [ { "id": "Division-of-Biology-and-Biological-Engineering" } ] }, "doi": "10.1101/2022.06.22.497261", "primary_object": { "basename": "2022.06.22.497261v2.full.pdf", "url": "https://authors.library.caltech.edu/records/k125e-vv934/files/2022.06.22.497261v2.full.pdf" }, "resource_type": "monograph", "pub_year": "2022", "author_list": "Siepe, Dirk H.; Henneberg, Lukas T.; et el." }, { "id": "https://authors.library.caltech.edu/records/yzpx8-sdg87", "eprint_id": 96672, "eprint_status": "archive", "datestamp": "2023-08-19 16:22:31", "lastmod": "2023-10-20 21:25:32", "type": "monograph", "metadata_visibility": "show", "creators": { "items": [ { "id": "Menon-K-P", "name": { "family": "Menon", "given": "Kaushiki P." }, "orcid": "0000-0003-1039-4704" }, { "id": "Kulkarni-V", "name": { "family": "Kulkarni", "given": "Vivek" } }, { "id": "Takemura-Shin-ya", "name": { "family": "Takemura", "given": "Shin-ya" }, "orcid": "0000-0003-2400-6426" }, { "id": "Anaya-M", "name": { "family": "Anaya", "given": "Michael" }, "orcid": "0000-0002-6944-3614" }, { "id": "Zinn-K", "name": { "family": "Zinn", "given": "Kai" }, "orcid": "0000-0002-6706-5605" } ] }, "title": "Interactions with presynaptic photoreceptors mediated by the Dpr11 and DIP-\u03b3 cell surface proteins control selection and survival of Drosophila amacrine neurons", "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\nbioRxiv preprint first posted online Jun. 22, 2019. \n\nWe thank Maximilien Courgeon and Claude Desplan for sharing unpublished antibodies and fly lines and for discussions, Larry Zipursky for sharing unpublished fly lines, comments on the manuscript and discussions, and Tim Mosca for his ExM protocol. We thank Violana Nesterova for figure preparation, Shuwa Xu for comments on the manuscript and discussions during the course of the work and Namrata Bali for help with ExM. The\ndpr11 RNAi stock was obtained from the Vienna Drosophila Resource Center (VDRC, www.vdrc.at). Stocks obtained from the Bloomington Drosophila Stock Center (NIHP40OD018537) were used in this study. Imaging was performed in the Biological Imaging Facility, with the support of the Caltech Beckman Institute and the Arnold and Mabel Beckman Foundation. Anti-Pros MR1A (mouse 1:4), anti-Elav 7E8A10 (rat, 1:10), anti-Dac 2-3 (mouse 1:50), anti-chaoptin 24B10 (mouse 1:20) were obtained from the Developmental Studies Hybridoma Bank (University of Iowa, IA). This work was supported\nby NIH grants RO1 EY028116 and R37 NS28182 to K. Z, and by the Howard Hughes Medical Institute (S-Y. T). \n\nAuthor contributions: Kaushiki P. Menon, Conceptualization, Supervision, Formal analysis, Validation, Investigation, Visualization, Methodology, Writing\u2014original draft, Writing\u2014review and editing; Vivek Kulkarni, Formal analysis, Validation, Investigation, Visualization, Methodology, Writing\u2014review and editing; Shin-ya Takemura, Formal analysis, Validation, Investigation, Visualization, Writing\u2014review and editing; Michael Anaya, Resources; Kai Zinn, Conceptualization, Supervision, Funding acquisition, Writing\u2014original draft, Writing\u2014 review and editing, Project administration.\n\nSubmitted - 679704.full.pdf
Supplemental Material - media-1.mp4
Supplemental Material - media-10.mp4
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Supplemental Material - media-4.mp4
Supplemental Material - media-5.mp4
Supplemental Material - media-6.mp4
Supplemental Material - media-7.mp4
Supplemental Material - media-8.mp4
Supplemental Material - media-9.mp4
", "abstract": "Drosophila R7 UV photoreceptors (PRs) are divided into yellow (y) and pale (p) subtypes with different wavelength sensitivities. yR7 PRs express the Dpr11 cell surface protein and are presynaptic to Dm8 amacrine neurons (yDm8) that express Dpr11's binding partner DIP-\u03b3, while pR7 PRs synapse onto DIP-\u03b3-negative pDm8 neurons. Dpr11 and DIP-\u03b3 expression patterns define yellow and pale medulla color vision circuits that project to higher-order areas. DIP- \u03b3 and dpr11 mutations affect the morphology of yDm8 arbors in the yellow circuit. yDm8 neurons are generated in excess during development and compete for presynaptic yR7 partners. Transsynaptic interactions between Dpr11 and DIP-\u03b3 are required for generation of neurotrophic signals that allow yDm8 neurons to survive. yDm8 and pDm8 neurons do not normally compete for neurotrophic support, but can be forced to do so by manipulating R7 subtype fates. DIP-\u03b3-Dpr11 interactions allow yDm8 neurons to select yR7 PRs as their home column partners.", "date": "2019-06-25", "date_type": "published", "id_number": "CaltechAUTHORS:20190624-141606104", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20190624-141606104", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "P40OD018537" }, { "agency": "Caltech Beckman Institute" }, { "agency": "Arnold and Mabel Beckman Foundation" }, { "agency": "NIH", "grant_number": "RO1 EY028116" }, { "agency": "NIH", "grant_number": "R37 NS28182" }, { "agency": "Howard Hughes Medical Institute (HHMI)" } ] }, "doi": "10.1101/679704", "primary_object": { "basename": "media-5.mp4", "url": "https://authors.library.caltech.edu/records/yzpx8-sdg87/files/media-5.mp4" }, "related_objects": [ { "basename": "media-7.mp4", "url": "https://authors.library.caltech.edu/records/yzpx8-sdg87/files/media-7.mp4" }, { "basename": "media-8.mp4", "url": "https://authors.library.caltech.edu/records/yzpx8-sdg87/files/media-8.mp4" }, { "basename": "media-9.mp4", "url": "https://authors.library.caltech.edu/records/yzpx8-sdg87/files/media-9.mp4" }, { "basename": "media-1.mp4", "url": "https://authors.library.caltech.edu/records/yzpx8-sdg87/files/media-1.mp4" }, { "basename": "media-3.mp4", "url": "https://authors.library.caltech.edu/records/yzpx8-sdg87/files/media-3.mp4" }, { "basename": "media-4.mp4", "url": "https://authors.library.caltech.edu/records/yzpx8-sdg87/files/media-4.mp4" }, { "basename": "media-6.mp4", "url": "https://authors.library.caltech.edu/records/yzpx8-sdg87/files/media-6.mp4" }, { "basename": "679704.full.pdf", "url": "https://authors.library.caltech.edu/records/yzpx8-sdg87/files/679704.full.pdf" }, { "basename": "media-10.mp4", "url": "https://authors.library.caltech.edu/records/yzpx8-sdg87/files/media-10.mp4" }, { "basename": "media-2.mp4", "url": "https://authors.library.caltech.edu/records/yzpx8-sdg87/files/media-2.mp4" } ], "resource_type": "monograph", "pub_year": "2019", "author_list": "Menon, Kaushiki P.; Kulkarni, Vivek; et el." }, { "id": "https://authors.library.caltech.edu/records/f70n0-njb82", "eprint_id": 67094, "eprint_status": "archive", "datestamp": "2023-08-20 11:06:19", "lastmod": "2023-10-18 20:05:13", "type": "monograph", "metadata_visibility": "show", "creators": { "items": [ { "id": "Al-Anzi-B", "name": { "family": "Al-Anzi", "given": "Bader" } }, { "id": "Olsman-N", "name": { "family": "Olsman", "given": "Noah" }, "orcid": "0000-0002-4351-3880" }, { "id": "Ormerod-C-M", "name": { "family": "Ormerod", "given": "Christopher" } }, { "id": "Gerges-S", "name": { "family": "Gerges", "given": "Sherif" } }, { "id": "Piliouras-G", "name": { "family": "Piliouras", "given": "Georgios" } }, { "id": "Ormerod-J", "name": { "family": "Ormerod", "given": "John" } }, { "id": "Zinn-K", "name": { "family": "Zinn", "given": "Kai" }, "orcid": "0000-0002-6706-5605" } ] }, "title": "A new computational model captures fundamental architectural features of diverse biological networks", "ispublished": "unpub", "full_text_status": "public", "note": "The copyright holder for this preprint is the author/funder. All rights reserved. No reuse allowed without permission. \n\nbioRxiv preprint first posted online Apr. 2, 2016. \n\nThis work was supported by a grant from the NIH, R21NS083874, to K. Z., and by the Della Martin Foundation. We also like to acknowledge NVIDIA Corporation for generously donating the NVIDIA GTX980 Graphics Card used in this study.\n\nSubmitted - 046813.full.pdf
", "abstract": "Complex biological systems are often represented by network graphs. However, their structural features are not adequately captured by existing computational graph models, perhaps because the datasets used to assemble them are incomplete and contain elements that lack shared functions. Here, we analyze three large, near-complete networks that produce specific cellular or behavioral outputs: a molecular yeast mitochondrial regulatory protein network, and two anatomical networks of very different scale, the mouse brain mesoscale connectivity network, and the C. elegans neuronal network. Surprisingly, these networks share similar characteristics. All consist of large communities composed of modules with general functions, and topologically distinct subnetworks spanning modular boundaries responsible for their more specific phenotypical outputs. We created a new model, SBM-PS, which generates networks by combining communities, followed by adjustment of connections by a path selection mechanism. This model captures fundamental architectural features that are common to the three networks.", "date": "2016-05-16", "date_type": "published", "id_number": "CaltechAUTHORS:20160516-072304246", "official_url": "https://resolver.caltech.edu/CaltechAUTHORS:20160516-072304246", "rights": "No commercial reproduction, distribution, display or performance rights in this work are provided.", "funders": { "items": [ { "agency": "NIH", "grant_number": "R21NS083874" }, { "agency": "Della Martin Foundation" }, { "agency": "NVIDIA" } ] }, "doi": "10.1101/046813", "primary_object": { "basename": "046813.full.pdf", "url": "https://authors.library.caltech.edu/records/f70n0-njb82/files/046813.full.pdf" }, "resource_type": "monograph", "pub_year": "2016", "author_list": "Al-Anzi, Bader; Olsman, Noah; et el." } ]