Mena binds α5 integrin directly and modulates α5β1 function.
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.
The David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Stephanie L
SL
Gupton
Daisy
D
Riquelme
Shannon K
SK
Hughes-Alford
Jenny
J
Tadros
Shireen S
SS
Rudina
Richard O
RO
Hynes
Douglas
D
Lauffenburger
Frank B
FB
Gertler
D000818:Animals; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000201:enzymology / Q000378:metabolism; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D022001:Focal Adhesions / Q000502:physiology*; D006801:Humans; D039482:Integrin alpha5 / Q000378:metabolism*; D039081:Integrin alpha5beta1 / Q000378:metabolism*; D051379:Mice; D008817:Mice, Mutant Strains; D008840:Microfilament Proteins; D041681:NIH 3T3 Cells; D011247:Pregnancy; D021381:Protein Transport / Q000502:physiology; D051381:Rats; D015398:Signal Transduction / Q000502:physiology*
D003598:Cytoskeletal Proteins; C102176:Enah protein, mouse; D039482:Integrin alpha5; D039081:Integrin alpha5beta1; D008840:Microfilament Proteins; D051416:Focal Adhesion Protein-Tyrosine Kinases