Association between ?4 integrin cytoplasmic tail and non-muscle myosin IIA regulates cell migration.

ABSTRACT: ?4?1 integrin regulates cell migration via cytoplasmic interactions. Here, we report an association between the cytoplasmic tail of ?4 integrin (?4 tail) and non-muscle myosin IIA (MIIA), demonstrated by co-immunoprecipitation of the MIIA heavy chain (HC) with anti-?4-integrin antibodies and pull-down of MIIA-HC with recombinant ?4 tail from cell lysates. The association between the ?4 tail and MIIA does not require paxillin binding or phosphorylation at Ser988 in the ?4 tail. We found that substituting Glu982 in the ?4 tail with alanine (E982A) disrupts the ?4-MIIA association without interfering with the paxillin binding or Ser988 phosphorylation. By comparing stably transfected CHO cells, we show that the E982A mutation reduces the ability of ?4?1 integrin to mediate cell spreading and to promote front-back polarization. In addition, we show that E982A impairs shear-flow-induced migration of the ?4-integrin-expressing CHO cells by reducing their migration speed and directional persistence. The E982A mutation also leads to defects in the organization of MIIA filament bundles. Furthermore, when cells are plated on fibronectin and simulated with shear flow, ?4?1 integrin forms filament-like patterns that co-align with MIIA filament bundles. These results provide a new mechanism for linking integrins to the actomyosin cytoskeleton and for regulating cell migration by integrins and non-muscle myosin II.

SUBMITTER: Rivera Rosado LA 

PROVIDER: S-EPMC3022002 | biostudies-literature | 2011 Feb

REPOSITORIES: biostudies-literature