Migfilin and Mig-2 link focal adhesions to filamin and the actin cytoskeleton and function in cell shape modulation.
Cell-extracellular matrix adhesion is an important determinant of cell morphology. We show here that migfilin, a LIM-containing protein, localizes to cell-matrix adhesions, associates with actin filaments, and is essential for cell shape modulation. Migfilin interacts with the cell-matrix adhesion protein Mig-2 (mitogen inducible gene-2), a mammalian homolog of UNC-112, and the actin binding protein filamin through its C- and N-terminal domains, respectively. Loss of Mig-2 or migfilin impairs cell shape modulation. Mig-2 recruits migfilin to cell-matrix adhesions, while the interaction with filamin mediates the association of migfilin with actin filaments. Migfilin therefore functions as an important scaffold at cell-matrix adhesions. Together, Mig-2, migfilin and filamin define a connection between cell matrix adhesions and the actin cytoskeleton and participate in the orchestration of actin assembly and cell shape modulation.
Tu
Yizeng
Y
Department of Pathology, University of Pittsburgh, Pittsburgh, PA 15261, USA.
Wu
Shan
S
Shi
Xiaohua
X
Chen
Ka
K
Wu
Chuanyue
C
D008841:Actin Cytoskeleton / Q000378:metabolism*; D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D001483:Base Sequence / Q000235:genetics; D016466:CHO Cells; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000302:isolation & purification*; D003285:Contractile Proteins / Q000378:metabolism*; D006224:Cricetinae; D003598:Cytoskeletal Proteins; D003599:Cytoskeleton / Q000378:metabolism; D018076:DNA, Complementary / Q000032:analysis / Q000235:genetics; D005057:Eukaryotic Cells / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism*; D064448:Filamins; D022001:Focal Adhesions / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008840:Microfilament Proteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D051381:Rats; D014407:Tumor Cells, Cultured; D020744:rac GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
D029742:Caenorhabditis elegans Proteins; D015815:Cell Adhesion Molecules; D003285:Contractile Proteins; D003598:Cytoskeletal Proteins; D018076:DNA, Complementary; C473794:FBLIM1 protein, human; D064448:Filamins; D008840:Microfilament Proteins; C442327:Mig-2 protein, C elegans; D020744:rac GTP-Binding Proteins