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Updated: Oct 20, 2025

Methods to Study Mrp4-containing Macromolecular Complexes in the Regulation of Fibroblast Migration
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ARHGAP4-SEPT2-SEPT9 complex enables both up- and down-modulation of integrin-mediated focal adhesions, cell

Na Kang1, Tsubasa S Matsui1, Shiyou Liu1

  • 1Division of Bioengineering, Graduate School of Engineering Science, Osaka University, Osaka 560-8531, Japan.

Molecular Biology of the Cell
|September 15, 2021
PubMed

Insights

Rho-GTPase-activating proteins (Rho-GAPs) regulate cell behavior. This study reveals ARHGAP4 forms a complex with SEPT2 and SEPT9, impacting cell migration and invasion by modulating focal adhesions and Integrin Beta 1 expression.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Rho family GTPases are crucial regulators of cellular processes.
  • Rho-GTPase-activating proteins (Rho-GAPs) inactivate Rho GTPases, but their signaling pathways are not fully understood.
  • Integrin-mediated focal adhesions (FAs) play key roles in cell adhesion, migration, and invasion.

Purpose of the Study:

  • To elucidate the signaling mechanisms of Rho-GTPase-activating proteins (Rho-GAPs).
  • To investigate the role of ARHGAP4 in regulating focal adhesions and cell behavior.
  • To identify novel protein complexes involved in cell migration and invasion.

Main Methods:

  • Co-immunoprecipitation to identify protein complex formation.
  • Silencing and overexpression of genes (ARHGAP4, SEPT2, SEPT9) to study their effects.
  • Immunofluorescence microscopy to visualize focal adhesion organization and Integrin Beta 1 expression.
  • Cell migration and invasion assays.

Main Results:

  • ARHGAP4 forms a complex with SEPT2 and SEPT9 through its Rho-GAP and SH3 domains.
  • Perturbations to the ARHGAP4-SEPT2-SEPT9 complex (silencing ARHGAP4 or overexpressing SEPT2/SEPT9) reorganize FAs and upregulate Integrin Beta 1.
  • These perturbations enhance cell migration and invasion, but FA clustering depends on microenvironmental ligands for Integrin Beta 1.
  • FA reorganization and cell migration/invasion changes can occur independently of enhanced FA clustering.

Conclusions:

  • ARHGAP4, SEPT2, and SEPT9 form a novel complex that modulates integrin-mediated focal adhesions.
  • This complex plays a critical role in regulating cell migration and invasion.
  • The study highlights the context-dependent nature of phenotypic changes, influenced by microenvironmental factors and Integrin Beta 1 signaling.

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