title: Integrin-β5 and zyxin mediate formation of ventral stress fibers in response to transforming growth factor β.
abstract: Cell adhesion to the extracellular matrix is an essential element of various biological processes. TGF-β cytokines regulate the matrix components and cell-matrix adhesions. The present study investigates the molecular organization of TGF-β-induced matrix adhesions. The study demonstrates that in various mouse and human epithelial cells TGF-β induces cellular structures containing 2 matrix adhesions bridged by a stretch of actin fibers. These structures are similar to ventral stress fibers (VSFs). Suppression of integrin-β5 by RNA interference reduces VSFs in majority of cells (> 75%), while overexpression of integrin-β5 fragments revealed a critical role of a distinct sequence in the cytoplasmic domain of integrin-β5 in the VSF structures. In addition, the integrity of actin fibers and Src kinase activity contribute to integrin-β5-mediated signaling and VSF formation. TGF-β-Smad signaling upregulates actin-regulatory proteins, such as caldesmon, zyxin, and zyxin-binding protein Csrp1 in mouse and human epithelial cells. Suppression of zyxin markedly inhibits formation of VSFs in response to TGF-β and integrin-β5. Zyxin is localized at actin fibers and matrix adhesions of VSFs and might bridge integrin-β5-mediated adhesions to actin fibers. These findings provide a platform for defining the molecular mechanism regulating the organization and activities of VSFs in response to TGF-β.
authors.affiliation: Department of Cancer Genetics; Roswell Park Cancer Institute; Buffalo, NY USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Bianchi-Smiraglia
authors.forename: Dimiter
authors.initials: D
authors.lastname: Kunnev
authors.forename: Michelle
authors.initials: M
authors.lastname: Limoge
authors.forename: Amy
authors.initials: A
authors.lastname: Lee
authors.forename: Mary C
authors.initials: MC
authors.lastname: Beckerle
authors.forename: Andrei V
authors.initials: AV
authors.lastname: Bakin
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002448:Cell Adhesion; D002460:Cell Line; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D005260:Female; D022001:Focal Adhesions / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D005786:Gene Expression Regulation; D006801:Humans; D039641:Integrin beta Chains / Q000235:genetics / Q000378:metabolism*; D060588:LIM Domain Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D051785:Smad Proteins / Q000235:genetics / Q000378:metabolism; D022502:Stress Fibers / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D060589:Zyxin / Q000235:genetics / Q000378:metabolism*
chemical_list: C558428:CSRP1 protein, human; D039641:Integrin beta Chains; D060588:LIM Domain Proteins; D009687:Nuclear Proteins; D051785:Smad Proteins; D016212:Transforming Growth Factor beta; D060589:Zyxin; C084344:integrin beta5
keywords: TGF-beta; adhesion; epithelial-mesenchymal transition; integrin; ventral stress-fibers; zyxin
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