title: CD2AP links cortactin and capping protein at the cell periphery to facilitate formation of lamellipodia.
abstract: Understanding the physiology of complex relationships between components of signaling pathways and the actin cytoskeleton is an important challenge. CD2AP is a membrane scaffold protein implicated in a variety of physiological and disease processes. The physiological function of CD2AP is unclear, but its biochemical interactions suggest that it has a role in dynamic actin assembly. Here, we report that CD2AP functions to facilitate the recruitment of actin capping protein (CP) to the Src kinase substrate, cortactin, at the cell periphery, and that this is necessary for formation of the short branched filaments that characterize lamellipodium formation and are required for cell migration. Superresolution fluorescence microscopy demonstrated that the efficient colocalization of CP and cortactin at the cell periphery required CD2AP. As both cortactin and CP function to enhance branched actin filament formation, CD2AP functions synergistically to enhance the function of both proteins. Our data demonstrate how the interplay between specialized actin regulatory molecules shapes the actin cytoskeleton.
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.
authors.forename: Jianping
authors.initials: J
authors.lastname: Zhao
authors.forename: Serawit
authors.initials: S
authors.lastname: Bruck
authors.forename: Saso
authors.initials: S
authors.lastname: Cemerski
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: Boyd
authors.initials: B
authors.lastname: Butler
authors.forename: Adish
authors.initials: A
authors.lastname: Dani
authors.forename: John A
authors.initials: JA
authors.lastname: Cooper
authors.forename: Andrey S
authors.initials: AS
authors.lastname: Shaw
mesh_terms: D051344:Actin Capping Proteins / Q000235:genetics / Q000378:metabolism*; D000199:Actins / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002465:Cell Movement; D051356:Cortactin / Q000235:genetics / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008817:Mice, Mutant Strains; D050199:Podocytes / Q000166:cytology* / Q000378:metabolism; D011554:Pseudopodia / Q000378:metabolism*; D018909:src Homology Domains; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D051344:Actin Capping Proteins; D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; C114545:CD2-associated protein; D051356:Cortactin; C495869:Cttn protein, mouse; D003598:Cytoskeletal Proteins; D019061:src-Family Kinases