title: The Arf GTPase-activating Protein, ASAP1, Binds Nonmuscle Myosin 2A to Control Remodeling of the Actomyosin Network.
abstract: ASAP1 regulates F-actin-based structures and functions, including focal adhesions (FAs) and circular dorsal ruffles (CDRs), cell spreading and migration. ASAP1 function requires its N-terminal BAR domain. We discovered that nonmuscle myosin 2A (NM2A) directly bound the BAR-PH tandem of ASAP1in vitro ASAP1 and NM2A co-immunoprecipitated and colocalized in cells. Knockdown of ASAP1 reduced colocalization of NM2A and F-actin in cells. Knockdown of ASAP1 or NM2A recapitulated each other's effects on FAs, cell migration, cell spreading, and CDRs. The NM2A-interacting BAR domain contributed to ASAP1 control of cell spreading and CDRs. Exogenous expression of NM2A rescued the effect of ASAP1 knockdown on CDRs but ASAP1 did not rescue NM2A knockdown defect in CDRs. Our results support the hypothesis that ASAP1 is a positive regulator of NM2A. Given other binding partners of ASAP1, ASAP1 may directly link signaling and the mechanical machinery of cell migration.
authors.affiliation: From the Laboratory of Cellular and Molecular Biology and.
authors.forename: Pei-Wen
authors.initials: PW
authors.lastname: Chen
authors.affiliation: From the Laboratory of Cellular and Molecular Biology and.
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Jian
authors.affiliation: Laboratory of Molecular Physiology and.
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Heissler
authors.affiliation: Cardiovascular and Pulmonary Branch, NHLBI, National Institutes of Health, Bethesda, Maryland 20892.
authors.forename: Kang
authors.initials: K
authors.lastname: Le
authors.affiliation: From the Laboratory of Cellular and Molecular Biology and.
authors.forename: Ruibai
authors.initials: R
authors.lastname: Luo
authors.affiliation: Laboratory of Cell Biology, NCI and.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Jenkins
authors.affiliation: Laboratory of Molecular Physiology and.
authors.forename: Attila
authors.initials: A
authors.lastname: Nagy
authors.affiliation: Cardiovascular and Pulmonary Branch, NHLBI, National Institutes of Health, Bethesda, Maryland 20892.
authors.forename: Joel
authors.initials: J
authors.lastname: Moss
authors.affiliation: Laboratory of Molecular Physiology and.
authors.forename: James R
authors.initials: JR
authors.lastname: Sellers
authors.affiliation: From the Laboratory of Cellular and Molecular Biology and randazzp@mail.nih.gov.
authors.forename: Paul A
authors.initials: PA
authors.lastname: Randazzo
mesh_terms: D000205:Actomyosin / Q000235:genetics / Q000378:metabolism*; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002465:Cell Movement / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D041681:NIH 3T3 Cells; D024507:Nonmuscle Myosin Type IIA / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D015398:Signal Transduction / Q000502:physiology*
chemical_list: C117891:ASAP1 protein, human; D048868:Adaptor Proteins, Signal Transducing; C485546:Asap1 protein, mouse; D000205:Actomyosin; D024507:Nonmuscle Myosin Type IIA
keywords: ADP ribosylation factor (ARF); GTPase-activating protein (GAP); actin; cell biology; cell migration; cytoskeleton; myosin