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Calpain2 mediates Rab5-driven focal adhesion disassembly and cell migration

Pablo A Mendoza1,2, Patricio Silva1,3, Jorge Díaz1,4

  • 1a Institute for Research in Dental Sciences, Faculty of Dentistry, Universidad de Chile , Santiago , Chile.

Cell Adhesion & Migration
|November 4, 2017
PubMed

Insights

Early endosome protein Rab5 enhances cell migration by promoting focal adhesion disassembly. Rab5 stimulates calpain2 activity, a key protease, leading to talin cleavage and increased cell motility.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Cancer Research

Background:

  • Rab5, an early endosome protein, is implicated in cell migration.
  • Focal adhesion disassembly is crucial for cell migration and involves talin proteolysis by calpain2.
  • Calpain2 localization to endosomal compartments suggests a role in Rab5-mediated processes.

Purpose of the Study:

  • To investigate the mechanism by which Rab5 promotes cell migration.
  • To determine if Rab5 regulates calpain2 activity and focal adhesion disassembly.

Main Methods:

  • Co-localization and co-immunoprecipitation assays to study Rab5 and calpain2 interaction.
  • Rab5 knockdown to assess its effect on calpain2 localization and activity.
  • Measurement of calpain2 activity using fluorogenic substrates and endogenous talin cleavage.
  • Assessment of focal adhesion disassembly and cell migration upon Rab5 expression and calpain2 inhibition.

Main Results:

  • Rab5 co-localizes with early endosomes and interacts with calpain2.
  • Rab5 knockdown reduces calpain2 accumulation at early endosomes and decreases its activity.
  • Rab5 expression accelerates focal adhesion disassembly, which is dependent on calpain2 activity.
  • Calpain2 inhibition blocks Rab5-induced focal adhesion disassembly and cell migration.

Conclusions:

  • Rab5 is a novel regulator of calpain2 activity.
  • Rab5 promotes focal adhesion proteolysis via calpain2, thereby facilitating cell migration.
  • This study elucidates a new molecular mechanism linking endosomal trafficking to cell motility.
Keywords:
Rab5calpain2early endosomefocal adhesionproteolysis

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