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Tricalbin-Mediated Contact Sites Control ER Curvature to Maintain Plasma Membrane Integrity

Collado, J; Kalemanov, M; Campelo, F; Bourgoint, C; Thomas, F; Loewith, R; Martínez-Sánchez, A; ... Fernández-Busnadiego, R; + view all (2019) Tricalbin-Mediated Contact Sites Control ER Curvature to Maintain Plasma Membrane Integrity. Developmental Cell , 51 (4) 476-487.e7. 10.1016/j.devcel.2019.10.018. Green open access

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Abstract

Membrane contact sites (MCS) between the endoplasmic reticulum (ER) and the plasma membrane (PM) play fundamental roles in all eukaryotic cells. ER-PM MCS are particularly abundant in Saccharomyces cerevisiae, where approximately half of the PM surface is covered by cortical ER (cER). Several proteins, including Ist2, Scs2/22, and Tcb1/2/3 are implicated in cER formation, but the specific roles of these molecules are poorly understood. Here, we use cryo-electron tomography to show that ER-PM tethers are key determinants of cER morphology. Notably, Tcb proteins (tricalbins) form peaks of extreme curvature on the cER membrane facing the PM. Combined modeling and functional assays suggest that Tcb-mediated cER peaks facilitate the transport of lipids between the cER and the PM, which is necessary to maintain PM integrity under heat stress. ER peaks were also present at other MCS, implying that membrane curvature enforcement may be a widespread mechanism to regulate MCS function.

Type: Article
Title: Tricalbin-Mediated Contact Sites Control ER Curvature to Maintain Plasma Membrane Integrity
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.devcel.2019.10.018
Publisher version: https://doi.org/10.1016/j.devcel.2019.10.018
Language: English
Additional information: © 2019 The Author(s). Published by Elsevier Inc.This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Keywords: cryo-ET, cryo-FIB, cryo-electron tomography, cryo-focused ion beam milling, endoplasmic reticulum, membrane contact site, membrane curvature, plasma membrane, tricalbins
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Lab for Molecular Cell Bio MRC-UCL
URI: https://discovery-pp.ucl.ac.uk/id/eprint/10086849
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