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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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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
|August 30, 2018
PubMed

Insights

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

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.

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