title: Identification of a novel inhibitory actin-capping protein binding motif in CD2-associated protein.
abstract: CD2-associated protein (CD2AP) is a scaffold molecule that plays a critical role in the maintenance of the kidney filtration barrier. Little, however, is understood about its mechanism of function. We used mass spectrometry to identify CD2AP-interacting proteins. Many of the proteins that we identified suggest a role for CD2AP in endocytosis and actin regulation. To address the role of CD2AP in regulation of the actin cytoskeleton, we focused on characterizing the interaction of CD2AP with actin-capping protein CP. We identified a novel binding motif LXHXTXXRPK(X)6P present in CD2AP that is also found in its homolog Cin85 and other capping protein-associated proteins such as CARMIL and CKIP-1. CD2AP inhibits the function of capping protein in vitro. Therefore, our results support a role of CD2AP in the regulation of the actin cytoskeleton.
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
authors.forename: Serawit
authors.initials: S
authors.lastname: Bruck
authors.forename: Tobias B
authors.initials: TB
authors.lastname: Huber
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Ingham
authors.forename: Kyoungtae
authors.initials: K
authors.lastname: Kim
authors.forename: Hanspeter
authors.initials: H
authors.lastname: Niederstrasser
authors.forename: Paul M
authors.initials: PM
authors.lastname: Allen
authors.forename: Tony
authors.initials: T
authors.lastname: Pawson
authors.forename: John A
authors.initials: JA
authors.lastname: Cooper
authors.forename: Andrey S
authors.initials: AS
authors.lastname: Shaw
mesh_terms: D000199:Actins / Q000737:chemistry*; D048868:Adaptor Proteins, Signal Transducing; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry; D002645:Chickens; D003598:Cytoskeletal Proteins; D003599:Cytoskeleton / Q000378:metabolism; D004705:Endocytosis; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008840:Microfilament Proteins / Q000737:chemistry; D008969:Molecular Sequence Data; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid
chemical_list: D000199:Actins; D048868:Adaptor Proteins, Signal Transducing; C114545:CD2-associated protein; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008840:Microfilament Proteins; C408877:PLEKHO1 protein, human; D011506:Proteins