title: Migfilin and filamin as regulators of integrin activation in endothelial cells and neutrophils.
abstract: Cell adhesion and migration depend on engagement of extracellular matrix ligands by integrins. Integrin activation is dynamically regulated by interactions of various cytoplasmic proteins, such as filamin and integrin activators, talin and kindlin, with the cytoplasmic tail of the integrin β subunit. Although filamin has been suggested to be an inhibitor of integrin activation, direct functional evidence for the inhibitory role of filamin is limited. Migfilin, a filamin-binding protein enriched at cell-cell and cell-extracellular matrix contact sites, can displace filamin from β1 and β3 integrins and promote integrin activation. However, its role in activation and functions of different β integrins in human vascular cells is unknown. In this study, using flow cytometry, we demonstrate that filamin inhibits β1 and αIIbβ3 integrin activation, and migfilin can overcome its inhibitory effect. Migfilin protein is widely expressed in different adherent and circulating blood cells and can regulate integrin activation in naturally-occurring vascular cells, endothelial cells and neutrophils. Migfilin can activate β1, β2 and β3 integrins and promote integrin mediated responses while migfilin depletion impairs the spreading and migration of endothelial cells. Thus, filamin can act broadly as an inhibitor and migfilin is a promoter of integrin activation.
authors: Department of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, United States of America.
authors: Mitali
authors: M
authors: Das
authors: Sujay Subbayya
authors: SS
authors: Ithychanda
authors: Jun
authors: J
authors: Qin
authors: Edward F
authors: EF
authors: Plow
mesh_terms: D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D003285:Contractile Proteins / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism*; D004730:Endothelium, Vascular; D064448:Filamins; D005434:Flow Cytometry; D006801:Humans; D039641:Integrin beta Chains / Q000378:metabolism; D016023:Integrins / Q000378:metabolism*; D008840:Microfilament Proteins / Q000378:metabolism*; D009504:Neutrophils / Q000378:metabolism*
chemical_list: D015815:Cell Adhesion Molecules; D003285:Contractile Proteins; D003598:Cytoskeletal Proteins; C473794:FBLIM1 protein, human; D064448:Filamins; D039641:Integrin beta Chains; D016023:Integrins; D008840:Microfilament Proteins