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Nat Cell Biol. 2018 Sep;20(9):1043-1051. doi: 10.1038/s41556-018-0150-z. Epub 2018 Aug 27.

Decrease in plasma membrane tension triggers PtdIns(4,5)P2 phase separation to inactivate TORC2.

Author information

1
Department of Molecular Biology, University of Geneva, Geneva, Switzerland.
2
Department of Biochemistry, University of Geneva, Geneva, Switzerland.
3
iGE3 Institute of Genetics and Genomics of Geneva, Geneva, Switzerland.
4
Swiss National Centre for Competence in Research Program Chemical Biology, Geneva, Switzerland.
5
Department of Organic Chemistry, University of Geneva, Geneva, Switzerland.
6
Department of Biochemistry, University of Geneva, Geneva, Switzerland. aurelien.roux@unige.ch.
7
Swiss National Centre for Competence in Research Program Chemical Biology, Geneva, Switzerland. aurelien.roux@unige.ch.
8
Department of Molecular Biology, University of Geneva, Geneva, Switzerland. robbie.loewith@unige.ch.
9
iGE3 Institute of Genetics and Genomics of Geneva, Geneva, Switzerland. robbie.loewith@unige.ch.
10
Swiss National Centre for Competence in Research Program Chemical Biology, Geneva, Switzerland. robbie.loewith@unige.ch.

Abstract

The target of rapamycin complex 2 (TORC2) plays a key role in maintaining the homeostasis of plasma membrane (PM) tension. TORC2 activation following increased PM tension involves redistribution of the Slm1 and 2 paralogues from PM invaginations known as eisosomes into membrane compartments containing TORC2. How Slm1/2 relocalization is triggered, and if/how this plays a role in TORC2 inactivation with decreased PM tension, is unknown. Using osmotic shocks and palmitoylcarnitine as orthogonal tools to manipulate PM tension, we demonstrate that decreased PM tension triggers spontaneous, energy-independent reorganization of pre-existing phosphatidylinositol-4,5-bisphosphate into discrete invaginated membrane domains, which cluster and inactivate TORC2. These results demonstrate that increased and decreased membrane tension are sensed through different mechanisms, highlighting a role for membrane lipid phase separation in mechanotransduction.

PMID:
30154550
DOI:
10.1038/s41556-018-0150-z

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