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A model for collagen secretion by intercompartmental continuities

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dc.contributor.author Bunel, Louis
dc.contributor.author Pincet, Lancelot
dc.contributor.author Malhotra, Vivek
dc.contributor.author Raote, Ishier
dc.contributor.author Pincet, Frederic
dc.date.accessioned 2024-02-14T10:58:10Z
dc.date.available 2024-02-14T10:58:10Z
dc.date.issued 2024
dc.identifier.citation Bunel L, Pincet L, Malhotra V, Raote I, Pincet F. A model for collagen secretion by intercompartmental continuities. Proc Natl Acad Sci U S A. 2024 Jan 2;121(1):e2310404120. DOI: 10.1073/pnas.2310404120
dc.identifier.issn 0027-8424
dc.identifier.uri http://hdl.handle.net/10230/59108
dc.description.abstract Newly synthesized secretory proteins are exported from the endoplasmic reticulum (ER) at specialized subcompartments called exit sites (ERES). Cargoes like procollagen are too large for export by the standard COPII-coated vesicle of 60 nm average diameter. We have previously suggested that procollagen is transported from the ER to the next secretory organelle, the ER-Golgi intermediate compartment (ERGIC), in TANGO1-dependent interorganelle tunnels. In the theoretical model presented here, we suggest that intrinsically disordered domains of TANGO1 in the ER lumen induce an entropic contraction, which exerts a force that draws procollagen toward the ERES. Within this framework, molecular gradients of pH and/or HSP47 between the ER and ERGIC create a force in the order of tens of femto-Newtons. This force is substantial enough to propel procollagen from the ER at a speed of approximately 1 nm · s-1. This calculated speed and the quantities of collagen secreted are similar to its observed physiological secretion rate in fibroblasts, consistent with the proposal that ER export is the rate-limiting step for procollagen secretion. Hence, the mechanism we propose is theoretically adequate to explain how cells can utilize molecular gradients and export procollagens at a rate commensurate with physiological needs.
dc.description.sponsorship This work was supported by the LiquOrg synergy grant, ERC-2020-SyG-951146, awarded to V.M. and F.P. V.M. acknowledges 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. I.R. acknowledges the support of Fondation pour la Recherche Médicale (grant AJE202210016216).
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher National Academy of Sciences
dc.relation.ispartof Proc Natl Acad Sci U S A. 2024 Jan 2;121(1):e2310404120
dc.rights © Copyright © 2023 the Author(s). Published by PNAS. This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/).
dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.title A model for collagen secretion by intercompartmental continuities
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.1073/pnas.2310404120
dc.subject.keyword TANGO1
dc.subject.keyword Collagen
dc.subject.keyword Entropic ratchet
dc.subject.keyword pH gradient
dc.subject.keyword Secretion
dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/951146
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion

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