title: Coronin 1C harbours a second actin-binding site that confers co-operative binding to F-actin.
abstract: Dynamic rearrangement of actin filament networks is critical for cell motility, phagocytosis and endocytosis. Coronins facilitate these processes, in part, by their ability to bind F-actin (filamentous actin). We previously identified a conserved surface-exposed arginine (Arg(30)) in the β-propeller of Coronin 1B required for F-actin binding in vitro and in vivo. However, whether this finding translates to other coronins has not been well defined. Using quantitative actin-binding assays, we show that mutating the equivalent residue abolishes F-actin binding in Coronin 1A, but not Coronin 1C. By mutagenesis and biochemical competition, we have identified a second actin-binding site in the unique region of Coronin 1C. Interestingly, leading-edge localization of Coronin 1C in fibroblasts requires the conserved site in the β-propeller, but not the site in the unique region. Furthermore, in contrast with Coronin 1A and Coronin 1B, Coronin 1C displays highly co-operative binding to actin filaments. In the present study, we highlight a novel mode of coronin regulation, which has implications for how coronins orchestrate cytoskeletal dynamics.
authors.affiliation: Lineberger Comprehensive Cancer Center, Chapel Hill, NC 27599, USA.
authors.forename: Keefe T
authors.initials: KT
authors.lastname: Chan
authors.forename: David W
authors.initials: DW
authors.lastname: Roadcap
authors.forename: Nicholas
authors.initials: N
authors.lastname: Holoweckyj
authors.forename: James E
authors.initials: JE
authors.lastname: Bear
mesh_terms: D000199:Actins / Q000378:metabolism*; D000818:Animals; D001120:Arginine / Q000235:genetics; D001665:Binding Sites; D002460:Cell Line; D006801:Humans; D051379:Mice; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D011485:Protein Binding; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D000199:Actins; D008840:Microfilament Proteins; D011994:Recombinant Proteins; C072061:coronin proteins; D001120:Arginine