Tetraspanin-8 sequesters syntaxin-2 to control biphasic release propensity of mucin granules

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• dc.contributor.author Wojnacki, José
• dc.contributor.author Lujan, Agustin Leonardo
• dc.contributor.author Brouwers, Nathalie
• dc.contributor.author Aranda Vallejo, Carla
• dc.contributor.author Bigliani, Gonzalo
• dc.contributor.author Pena Rodriguez, Maria
• dc.contributor.author Foresti, Ombretta
• dc.contributor.author Malhotra, Vivek
• dc.date.accessioned 2023-11-03T07:36:29Z
• dc.date.available 2023-11-03T07:36:29Z
• dc.date.issued 2023
• dc.description.abstract Agonist-mediated stimulated pathway of mucin and insulin release are biphasic in which rapid fusion of pre-docked granules is followed by slow docking and fusion of granules from the reserve pool. Here, based on a cell-culture system, we show that plasma membrane-located tetraspanin-8 sequesters syntaxin-2 to control mucin release. Tetraspanin-8 affects fusion of granules during the second phase of stimulated mucin release. The tetraspanin-8/syntaxin-2 complex does not contain VAMP-8, which functions with syntaxin-2 to mediate granule fusion. We suggest that by sequestering syntaxin-2, tetraspanin-8 prevents docking of granules from the reserve pool. In the absence of tetraspanin-8, more syntaxin-2 is available for docking and fusion of granules and thus doubles the quantities of mucins secreted. This principle also applies to insulin release and we suggest a cell type specific Tetraspanin/Syntaxin combination is a general mechanism regulating the fusion of dense core granules.
• dc.description.sponsorship We acknowledge the support of the Spanish Ministry of Science and Innovation to the EMBL partnership, the Centro de Excelencia Severo Ochoa, and the CERCA Programme / Generalitat de Catalunya. V.M. is an Institució Catalana de Recerca i Estudis Avançats professor at the Centre for Genomic Regulation. Work in the Malhotra lab is funded by grants from the Spanish Ministry of Economy and Competitiveness (Plan Nacional to V.M.: PID2019-105518GB-I00) and the European Union’s HORIZON under the grant agreements No. 894115 and No. 101062382. J.W. is funded by the European Research Council (H2020-MSCA-IF-2019-894115). A.L.L. is funded by the European Research Council (HORIZON-MSCA-2021-PF-101062382). This work reflects only the authors’ views, and the EU Community is not liable for any use that may be made of the information contained therein.
• dc.format.mimetype application/pdf
• dc.identifier.citation Wojnacki J, Lujan AL, Brouwers N, Aranda-Vallejo C, Bigliani G, Pena Rodriguez M, Foresti O, Malhotra V. Tetraspanin-8 sequesters syntaxin-2 to control biphasic release propensity of mucin granules. Nat Commun. 2023 Jun 22;14(1):3710. DOI: 10.1038/s41467-023-39277-9
• dc.identifier.doi http://dx.doi.org/10.1038/s41467-023-39277-9
• dc.identifier.issn 2041-1723
• dc.identifier.uri http://hdl.handle.net/10230/58202
• dc.language.iso eng
• dc.publisher Nature Research
• dc.relation.ispartof Nat Commun. 2023 Jun 22;14(1):3710
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/894115
• dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PID2019-105518GB-I00
• dc.relation.projectID info:eu-repo/grantAgreement/EC/HE/101062382
• dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/894115
• dc.rights © The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword Exocytosis
• dc.subject.keyword Secretion
• dc.subject.keyword SNARE
• dc.title Tetraspanin-8 sequesters syntaxin-2 to control biphasic release propensity of mucin granules
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion