A model for collagen secretion by intercompartmental continuities

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 procollag...

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Detalles Bibliográficos
Autores: Bunel, Louis, Pincet, Lancelot, Malhotra, Vivek, Raote, Ishier, Pincet, Frederic
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2024
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10230/59108
Acceso en línea:http://hdl.handle.net/10230/59108
http://dx.doi.org/10.1073/pnas.2310404120
Access Level:acceso abierto
Palabra clave:TANGO1
Collagen
Entropic ratchet
pH gradient
Secretion
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spelling A model for collagen secretion by intercompartmental continuitiesBunel, LouisPincet, LancelotMalhotra, VivekRaote, IshierPincet, FredericTANGO1CollagenEntropic ratchetpH gradientSecretionNewly 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.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).National Academy of Sciences202420242024info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/59108http://dx.doi.org/10.1073/pnas.2310404120reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésProc Natl Acad Sci U S A. 2024 Jan 2;121(1):e2310404120info:eu-repo/grantAgreement/EC/H2020/951146© 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/).http://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:10230/591082026-05-29T05:05:01Z
dc.title.none.fl_str_mv A model for collagen secretion by intercompartmental continuities
title A model for collagen secretion by intercompartmental continuities
spellingShingle A model for collagen secretion by intercompartmental continuities
Bunel, Louis
TANGO1
Collagen
Entropic ratchet
pH gradient
Secretion
title_short A model for collagen secretion by intercompartmental continuities
title_full A model for collagen secretion by intercompartmental continuities
title_fullStr A model for collagen secretion by intercompartmental continuities
title_full_unstemmed A model for collagen secretion by intercompartmental continuities
title_sort A model for collagen secretion by intercompartmental continuities
dc.creator.none.fl_str_mv Bunel, Louis
Pincet, Lancelot
Malhotra, Vivek
Raote, Ishier
Pincet, Frederic
author Bunel, Louis
author_facet Bunel, Louis
Pincet, Lancelot
Malhotra, Vivek
Raote, Ishier
Pincet, Frederic
author_role author
author2 Pincet, Lancelot
Malhotra, Vivek
Raote, Ishier
Pincet, Frederic
author2_role author
author
author
author
dc.subject.none.fl_str_mv TANGO1
Collagen
Entropic ratchet
pH gradient
Secretion
topic TANGO1
Collagen
Entropic ratchet
pH gradient
Secretion
description 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.
publishDate 2024
dc.date.none.fl_str_mv 2024
2024
2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10230/59108
http://dx.doi.org/10.1073/pnas.2310404120
url http://hdl.handle.net/10230/59108
http://dx.doi.org/10.1073/pnas.2310404120
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Proc Natl Acad Sci U S A. 2024 Jan 2;121(1):e2310404120
info:eu-repo/grantAgreement/EC/H2020/951146
dc.rights.none.fl_str_mv http://creativecommons.org/licenses/by-nc-nd/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv National Academy of Sciences
publisher.none.fl_str_mv National Academy of Sciences
dc.source.none.fl_str_mv reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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