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Association between α4 integrin cytoplasmic tail and non-muscle myosin IIA regulates cell migration

Leslie A Rivera Rosado1, Troy A Horn, Sara C McGrath

  • 1Department of Cell Biology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

Journal of Cell Science
|January 13, 2011
PubMed

Insights

Alpha4beta1 integrin associates with non-muscle myosin IIA (MIIA) via its cytoplasmic tail. This interaction is crucial for cell spreading, polarization, and migration, revealing a new mechanism for actomyosin cytoskeleton regulation.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biophysics

Background:

  • Integrins are key regulators of cell adhesion and migration.
  • The cytoplasmic tail of integrins mediates interactions with intracellular proteins.
  • Non-muscle myosin IIA (MIIA) is essential for cytoskeletal dynamics and cell motility.

Purpose of the Study:

  • To investigate the association between the cytoplasmic tail of alpha4beta1 integrin (α4 tail) and non-muscle myosin IIA (MIIA).
  • To elucidate the role of this interaction in regulating cell migration and cytoskeletal organization.

Main Methods:

  • Co-immunoprecipitation assays to detect protein-protein interactions.
  • Pull-down assays using recombinant proteins.
  • Site-directed mutagenesis (E982A) to disrupt the α4-MIIA association.
  • Cell-based assays measuring cell spreading, polarization, and migration under shear flow.
  • Microscopy to analyze MIIA filament organization.

Main Results:

  • Demonstrated a direct association between the α4 tail and MIIA heavy chain, independent of paxillin binding or Ser988 phosphorylation.
  • A specific mutation (E982A) disrupted the α4-MIIA interaction, leading to impaired cell spreading, front-back polarization, and shear-flow-induced migration.
  • The E982A mutation also caused defects in MIIA filament organization and altered the co-alignment of α4β1 integrin with MIIA filaments.

Conclusions:

  • The cytoplasmic tail of α4β1 integrin directly binds to MIIA, establishing a link to the actomyosin cytoskeleton.
  • This interaction is critical for regulating cell migration dynamics and cytoskeletal organization.
  • Provides a novel mechanism by which integrins control cell migration through MIIA-mediated contractility.

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