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TRPM4 Is a Novel Component of the Adhesome Required for Focal Adhesion Disassembly, Migration and Contractility

Mónica Cáceres1, Liliana Ortiz2, Tatiana Recabarren3

  • 1Programa de Biología Celular y Molecular, Instituto de Ciencias Biomédicas (ICBM), Facultad de Medicina, Universidad de Chile, Santiago, Chile; Department of Neurobiology, Physiology and Behavior, College of Biological Sciences, University of California Davis, Davis, California, United States of America.

Plos One
|June 26, 2015
PubMed

Insights

TRPM4 channels localize to focal adhesions, regulating cell migration and contractility. This discovery reveals TRPM4

Area of Science:

  • Cell Biology
  • Molecular Physiology
  • Biophysics

Background:

  • Cellular migration and contractility are crucial biological processes.
  • These processes involve complex regulation by cytoskeleton dynamics, focal adhesion turnover, and calcium (Ca2+) signaling.
  • TRPM4 is a Ca2+-activated non-selective cation channel (Ca2+-NSCC) permeable to monovalent ions.

Purpose of the Study:

  • To identify proteins associated with the TRPM4 channel.
  • To investigate the role of TRPM4 in cellular migration and contractility.
  • To determine the localization and function of TRPM4 at focal adhesions.

Main Methods:

  • Mass spectrometry-based proteomics to identify TRPM4-interacting proteins.
  • Cellular localization studies using immunofluorescence.
  • Functional assays measuring focal adhesion turnover, Ca2+ influx, and cellular behavior (spreading, migration, contractility).
  • In vivo studies on cutaneous wound healing.

Main Results:

  • Proteomics identified a significant number of actin cytoskeleton and focal adhesion-associated proteins interacting with TRPM4.
  • TRPM4 was localized to focal adhesions in various cell types.
  • TRPM4 suppression impaired focal adhesion turnover, reduced Ca2+ influx, altered FAK and Rac activity, and decreased cell migration and contractility.
  • TRPM4 inhibition negatively impacted in vivo cutaneous wound healing.

Conclusions:

  • TRPM4 is a novel TRP channel localized to focal adhesions.
  • TRPM4 plays a critical role in regulating cellular migration and contractility.
  • TRPM4 modulation impacts key signaling pathways and cellular behaviors, with implications for tissue repair.

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