title: Mammalian adenylyl cyclase-associated protein 1 (CAP1) regulates cofilin function, the actin cytoskeleton, and cell adhesion.
abstract: CAP (adenylyl cyclase-associated protein) was first identified in yeast as a protein that regulates both the actin cytoskeleton and the Ras/cAMP pathway. Although the role in Ras signaling does not extend beyond yeast, evidence supports that CAP regulates the actin cytoskeleton in all eukaryotes including mammals. In vitro actin polymerization assays show that both mammalian and yeast CAP homologues facilitate cofilin-driven actin filament turnover. We generated HeLa cells with stable CAP1 knockdown using RNA interference. Depletion of CAP1 led to larger cell size and remarkably developed lamellipodia as well as accumulation of filamentous actin (F-actin). Moreover, we found that CAP1 depletion also led to changes in cofilin phosphorylation and localization as well as activation of focal adhesion kinase (FAK) and enhanced cell spreading. CAP1 forms complexes with the adhesion molecules FAK and Talin, which likely underlie the cell adhesion phenotypes through inside-out activation of integrin signaling. CAP1-depleted HeLa cells also had substantially elevated cell motility as well as invasion through Matrigel. In summary, in addition to generating in vitro and in vivo evidence further establishing the role of mammalian CAP1 in actin dynamics, we identified a novel cellular function for CAP1 in regulating cell adhesion.
authors.affiliation: From the Department of Biological Sciences and; Molecular Biosciences Program, Arkansas State University, State University, Arkansas 72467.
authors.forename: Haitao
authors.initials: H
authors.lastname: Zhang
authors.affiliation: From the Department of Biological Sciences and; Molecular Biosciences Program, Arkansas State University, State University, Arkansas 72467.
authors.forename: Pooja
authors.initials: P
authors.lastname: Ghai
authors.affiliation: From the Department of Biological Sciences and.
authors.forename: Huhehasi
authors.initials: H
authors.lastname: Wu
authors.affiliation: the Shanghai Tenth People's Hospital of Tongji University, Shanghai 200072, China, and.
authors.forename: Changhui
authors.initials: C
authors.lastname: Wang
authors.affiliation: the Department of Pharmacology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104. Electronic address: jfield@upenn.edu.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Field
authors.affiliation: From the Department of Biological Sciences and; Molecular Biosciences Program, Arkansas State University, State University, Arkansas 72467,. Electronic address: gzhou@astate.edu.
authors.forename: Guo-Lei
authors.initials: GL
authors.lastname: Zhou
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism*; D051339:Actin Depolymerizing Factors / Q000378:metabolism*; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002448:Cell Adhesion; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000378:metabolism*; D002465:Cell Movement; D048430:Cell Shape; D048429:Cell Size; D003598:Cytoskeletal Proteins / Q000737:chemistry / Q000378:metabolism*; D004789:Enzyme Activation; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008322:Mammals / Q000378:metabolism*; D051379:Mice; D009361:Neoplasm Invasiveness; D010766:Phosphorylation; D011485:Protein Binding; D011554:Pseudopodia / Q000378:metabolism; D016608:Talin / Q000378:metabolism
chemical_list: D051339:Actin Depolymerizing Factors; C489549:CAP1 protein, human; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D016608:Talin; C525401:CAP1 cyclase-associated protein, mouse; D051417:Focal Adhesion Kinase 1
keywords: Actin; Cell Motility; Cell Signaling; Cofilin; Cytoskeleton