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

被引:104
作者
Riggi, Margot [1 ,2 ,3 ,4 ]
Niewola-Staszkowska, Karolina [1 ,4 ]
Chiaruttini, Nicolas [2 ]
Colom, Adai [2 ,4 ]
Kusmider, Beata [1 ]
Mercier, Vincent [2 ,4 ]
Soleimanpour, Saeideh [4 ,5 ]
Stahl, Michael [1 ]
Matile, Stefan [4 ,5 ]
Roux, Aurelien [2 ,4 ]
Loewith, Robbie [1 ,3 ,4 ]
机构
[1] Univ Geneva, Dept Mol Biol, Geneva, Switzerland
[2] Univ Geneva, Dept Biochem, Geneva, Switzerland
[3] iGE3 Inst Genet & Genom Geneva, Geneva, Switzerland
[4] Swiss Natl Ctr Competence Res Program Chem Biol, Geneva, Switzerland
[5] Univ Geneva, Dept Organ Chem, Geneva, Switzerland
基金
瑞士国家科学基金会; 欧洲研究理事会;
关键词
PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE CLUSTERS; RAPAMYCIN COMPLEX 2; SACCHAROMYCES-CEREVISIAE; ACTIN CYTOSKELETON; PROTEINS SLM1; CELL-SHAPE; YEAST; POLARIZATION; TARGET; ENDOCYTOSIS;
D O I
10.1038/s41556-018-0150-z
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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.
引用
收藏
页码:1043 / +
页数:11
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