title: Physical and functional association of migfilin with cell-cell adhesions.
abstract: Cell-cell junctions are essential for epithelial and endothelial tissue formation and communication between neighboring cells. We report here that migfilin, a recently identified component of cell-extracellular matrix adhesions, is recruited to cell-cell junctions in response to cadherin-mediated cell-cell adhesions. Migfilin is detected at cell-cell junctions in both epithelial and endothelial cells. It forms detergent-resistant, discrete clusters that associate with actin bundles bridging neighboring cells. Immunoelectron microscopic analyses reveal that migfilin is closely associated with beta-catenin, but not desmosomes, at cell-cell junctions. Furthermore, we show that the C-terminal LIM domains, but not its N-terminal domain, mediates migfilin localization to cell-cell junctions. The site mediating the localization of migfilin to cell-cell junctions at least partially overlaps with that mediating the localization of migfilin to cell-ECM adhesions. Finally, siRNA-mediated depletion of migfilin compromised the organization of adherens junctions and weakened cell-cell association. These results identify migfilin as a component of adherens junctions and suggest an important role for migfilin in the organization of the cell-cell adhesion structure.
authors.affiliation: Department of Pathology, Center for Biological Imaging, University of Pittsburgh, Pittsburgh, PA 15261, USA.
authors.forename: Vasiliki
authors.initials: V
authors.lastname: Gkretsi
authors.forename: Yongjun
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yizeng
authors.initials: Y
authors.lastname: Tu
authors.forename: Ka
authors.initials: K
authors.lastname: Chen
authors.forename: Donna B
authors.initials: DB
authors.lastname: Stolz
authors.forename: Yanqiang
authors.initials: Y
authors.lastname: Yang
authors.forename: Simon C
authors.initials: SC
authors.lastname: Watkins
authors.forename: Chuanyue
authors.initials: C
authors.lastname: Wu
mesh_terms: D008841:Actin Cytoskeleton / Q000737:chemistry; D015820:Cadherins / Q000378:metabolism; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000032:analysis* / Q000737:chemistry / Q000502:physiology; D003598:Cytoskeletal Proteins / Q000378:metabolism; D042783:Endothelial Cells / Q000737:chemistry; D004847:Epithelial Cells / Q000737:chemistry; D005109:Extracellular Matrix / Q000737:chemistry; D006801:Humans; D007365:Intercellular Junctions / Q000737:chemistry / Q000648:ultrastructure; D016253:Microscopy, Immunoelectron; D017434:Protein Structure, Tertiary; D015534:Trans-Activators / Q000378:metabolism; D051176:beta Catenin
chemical_list: C495270:CTNNB1 protein, human; D015820:Cadherins; D015815:Cell Adhesion Molecules; D003598:Cytoskeletal Proteins; C473794:FBLIM1 protein, human; D015534:Trans-Activators; D051176:beta Catenin