Mena binds α5 integrin directly and modulates α5β1 function.

TitleMena binds α5 integrin directly and modulates α5β1 function.
Publication TypeJournal Article
Year of Publication2012
AuthorsGupton, SL, Riquelme, D, Hughes-Alford, SK, Tadros, J, Rudina, SS, Hynes, RO, Lauffenburger, DA, Gertler, FB
JournalJ Cell Biol
Date Published2012 Aug 20
KeywordsAnimals, Cytoskeletal Proteins, Extracellular Matrix, Female, Fibroblasts, Focal Adhesion Protein-Tyrosine Kinases, Focal Adhesions, Humans, Integrin alpha5, Integrin alpha5beta1, Mice, Mice, Mutant Strains, NIH 3T3 Cells, Pregnancy, Protein Transport, Rats, Signal Transduction

Mena is an Ena/VASP family actin regulator with roles in cell migration, chemotaxis, cell-cell adhesion, tumor cell invasion, and metastasis. Although enriched in focal adhesions, Mena has no established function within these structures. We find that Mena forms an adhesion-regulated complex with α5β1 integrin, a fibronectin receptor involved in cell adhesion, motility, fibronectin fibrillogenesis, signaling, and growth factor receptor trafficking. Mena bound directly to the carboxy-terminal portion of the α5 cytoplasmic tail via a 91-residue region containing 13 five-residue "LERER" repeats. In fibroblasts, the Mena-α5 complex was required for "outside-in" α5β1 functions, including normal phosphorylation of FAK and paxillin and formation of fibrillar adhesions. It also supported fibrillogenesis and cell spreading and controlled cell migration speed. Thus, fibroblasts require Mena for multiple α5β1-dependent processes involving bidirectional interactions between the extracellular matrix and cytoplasmic focal adhesion proteins.

Alternate JournalJ. Cell Biol.
PubMed ID22908313
PubMed Central IDPMC3514034
Grant ListGM58801 / GM / NIGMS NIH HHS / United States
U54-CA112967 / CA / NCI NIH HHS / United States
/ / Howard Hughes Medical Institute / United States