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Single-molecule Super-resolution Imaging of Phosphatidylinositol 4,5-bisphosphate in the Plasma Membrane with Novel Fluorescent Probes
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Decrease in plasma membrane tension triggers PtdIns(4,5)P2 phase separation to inactivate TORC2.

Margot Riggi1,2,3,4, Karolina Niewola-Staszkowska1,4, Nicolas Chiaruttini2

  • 1Department of Molecular Biology, University of Geneva, Geneva, Switzerland.

Nature Cell Biology
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This summary is machine-generated.

Decreased plasma membrane tension inactivates TORC2 by reorganizing lipids into membrane domains, distinct from how increased tension activates it. This reveals lipid phase separation

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Area of Science:

  • Cell Biology
  • Membrane Biophysics
  • Mechanotransduction

Background:

  • The target of rapamycin complex 2 (TORC2) is crucial for maintaining plasma membrane (PM) tension homeostasis.
  • TORC2 activation by increased PM tension involves Slm1/2 paralogue redistribution from eisosomes.
  • The mechanisms of Slm1/2 relocalization and TORC2 inactivation under decreased PM tension remain unclear.

Purpose of the Study:

  • To investigate how Slm1/2 relocalization is triggered by changes in PM tension.
  • To elucidate the role of Slm1/2 relocalization in TORC2 inactivation during decreased PM tension.
  • To understand the distinct sensing mechanisms for increased versus decreased PM tension.

Main Methods:

  • Utilized osmotic shocks and palmitoylcarnitine to orthogonally manipulate PM tension.
  • Observed the reorganization of phosphatidylinositol-4,5-bisphosphate (PIP2) under decreased PM tension.
  • Investigated the clustering of these PIP2 domains and their effect on TORC2 activity.

Main Results:

  • Decreased PM tension triggers spontaneous, energy-independent reorganization of PIP2 into invaginated membrane domains.
  • These PIP2-rich domains cluster and lead to TORC2 inactivation.
  • Demonstrated distinct mechanisms for sensing increased and decreased PM tension.

Conclusions:

  • Plasma membrane tension is sensed differently under conditions of increased and decreased tension.
  • Phosphatidylinositol-4,5-bisphosphate reorganization and lipid phase separation play a key role in mechanotransduction.
  • Identified a novel mechanism for TORC2 inactivation mediated by lipid domain formation.