Migfilin interacts with vasodilator-stimulated phosphoprotein (VASP) and regulates VASP localization to cell-matrix adhesions and migration.
Cell migration is a complex process that is coordinately regulated by cell-matrix adhesion and actin cytoskeleton. We report here that migfilin, a recently identified component of cell-matrix adhesions, is a biphasic regulator of cell migration. Loss of migfilin impairs cell migration. Surprisingly, overexpression of migfilin also reduces cell migration. Molecularly, we have identified vasodilator-stimulated phosphoprotein (VASP) as a new migfilin-binding protein. The interaction is mediated by the VASP EVH1 domain and a single L104PPPPP site located within the migfilin proline-rich domain. Migfilin and VASP form a complex in both suspended and adhered cells, and in the latter, they co-localize in cell-matrix adhesions. Functionally, migfilin facilitates VASP localization to cell-matrix adhesions. Using two different approaches (VASP-binding defective migfilin mutants and small interfering RNA-mediated VASP knockdown), we show that the interaction with VASP is crucially involved in migfilin-mediated regulation of cell migration. Our results identify migfilin as an important regulator of cell migration and provide new information on the mechanism by which migfilin regulates this process.
Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA.
Yongjun
Y
Zhang
Yizeng
Y
Tu
Vasiliki
V
Gkretsi
Chuanyue
C
Wu
D000199:Actins / Q000737:chemistry; D000818:Animals; D001665:Binding Sites; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology*; D002465:Cell Movement; D003598:Cytoskeletal Proteins / Q000737:chemistry* / Q000378:metabolism; D004285:Dogs; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D008840:Microfilament Proteins / Q000737:chemistry / Q000502:physiology*; D009154:Mutation; D010750:Phosphoproteins / Q000737:chemistry / Q000502:physiology*; D017434:Protein Structure, Tertiary; D034741:RNA, Small Interfering / Q000378:metabolism; D000098662:Vasodilator-Stimulated Phosphoprotein
D000199:Actins; D015815:Cell Adhesion Molecules; D003598:Cytoskeletal Proteins; C473794:FBLIM1 protein, human; D008840:Microfilament Proteins; D010750:Phosphoproteins; D034741:RNA, Small Interfering; D000098662:Vasodilator-Stimulated Phosphoprotein