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Tricalbin proteins regulate plasma membrane phospholipid homeostasis

Thomas, Ffion B; Omnus, Deike J; Bader, Jakob M; Chung, Gary Hc; Kono, Nozomu; Stefan, Christopher J; (2022) Tricalbin proteins regulate plasma membrane phospholipid homeostasis. Life Science Alliance , 5 (8) , Article e202201430. 10.26508/lsa.202201430. Green open access

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Abstract

The evolutionarily conserved extended synaptotagmin (E-Syt) proteins are calcium-activated lipid transfer proteins that function at contacts between the ER and plasma membrane (ER-PM contacts). However, roles of the E-Syt family members in PM lipid organisation remain incomplete. Among the E-Syt family, the yeast tricalbin (Tcb) proteins are essential for PM integrity upon heat stress, but it is not known how they contribute to PM maintenance. Using quantitative lipidomics and microscopy, we find that the Tcb proteins regulate phosphatidylserine homeostasis at the PM. Moreover, upon heat-induced membrane stress, Tcb3 co-localises with the PM protein Sfk1 that is implicated in PM phospholipid asymmetry and integrity. The Tcb proteins also control the PM targeting of the known phosphatidylserine effector Pkc1 upon heat-induced stress. Phosphatidylserine has evolutionarily conserved roles in PM organisation, integrity, and repair. We propose that phospholipid regulation is an ancient essential function of E-Syt family members required for PM integrity.

Type: Article
Title: Tricalbin proteins regulate plasma membrane phospholipid homeostasis
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.26508/lsa.202201430
Publisher version: https://doi.org/10.26508/lsa.202201430
Language: English
Additional information: © 2022 Thomas et al. This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/).
Keywords: Cell Membrane, Homeostasis, Membrane Proteins, Phosphatidylserines, Phospholipids, Synaptotagmins
UCL classification: 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
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL
URI: https://discovery-pp.ucl.ac.uk/id/eprint/10147383
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