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Quantitative Measurement of Invadopodia-mediated Extracellular Matrix Proteolysis in Single and Multicellular Contexts
Published on: August 27, 2012
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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
Summary
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.
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