Identification of a novel inhibitory actin-capping protein binding motif in CD2-associated protein.
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.
Bruck
Serawit
S
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Huber
Tobias B
TB
Ingham
Robert J
RJ
Kim
Kyoungtae
K
Niederstrasser
Hanspeter
H
Allen
Paul M
PM
Pawson
Tony
T
Cooper
John A
JA
Shaw
Andrey S
AS
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
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