title: Clathrin potentiates vaccinia-induced actin polymerization to facilitate viral spread.
abstract: During their egress, newly assembled vaccinia virus particles fuse with the plasma membrane and enhance their spread by inducing Arp2/3-dependent actin polymerization. Investigating the events surrounding vaccinia virus fusion, we discovered that vaccinia transiently recruits clathrin in a manner dependent on the clathrin adaptor AP-2. The recruitment of clathrin to vaccinia dramatically enhances the ability of the virus to induce actin-based motility. We demonstrate that clathrin promotes clustering of the virus actin tail nucleator A36 and host N-WASP, which activates actin nucleation through the Arp2/3 complex. Increased clustering enhances N-WASP stability, leading to more efficient actin tail initiation and sustained actin polymerization. Our observations uncover an unexpected role for clathrin during virus spread and have important implications for the regulation of actin polymerization.
authors.affiliation: Cell Motility Laboratory, Cancer Research UK, London Research Institute, London WC2A 3LY, UK.
authors.forename: Ashley C
authors.initials: AC
authors.lastname: Humphries
authors.forename: Mark P
authors.initials: MP
authors.lastname: Dodding
authors.forename: David J
authors.initials: DJ
authors.lastname: Barry
authors.forename: Lucy M
authors.initials: LM
authors.lastname: Collinson
authors.forename: Charlotte H
authors.initials: CH
authors.lastname: Durkin
authors.forename: Michael
authors.initials: M
authors.lastname: Way
mesh_terms: D051376:Actin-Related Protein 2-3 Complex; D000199:Actins / Q000378:metabolism*; D002966:Clathrin / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D055503:Protein Multimerization; D014616:Vaccinia virus / Q000472:pathogenicity*; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal
chemical_list: D051376:Actin-Related Protein 2-3 Complex; D000199:Actins; D002966:Clathrin; C495771:WASL protein, human; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal