Identification of a novel inhibitory actin-capping protein binding motif in CD2-associated protein.

Serawit Bruck, Tobias B Huber, Robert J Ingham, Kyoungtae Kim, Hanspeter Niederstrasser, Paul M Allen, Tony Pawson, John A Cooper, Andrey S Shaw
Author Information
  1. Serawit Bruck: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.

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.

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Grants

  1. R01 GM038542/NIGMS NIH HHS
  2. T32 GM08492/NIGMS NIH HHS
  3. T32 GM008492/NIGMS NIH HHS
  4. R01 DK066428/NIDDK NIH HHS
  5. DK066428/NIDDK NIH HHS
  6. R01 GM038542-19/NIGMS NIH HHS

MeSH Term

Actins
Adaptor Proteins, Signal Transducing
Amino Acid Motifs
Amino Acid Sequence
Animals
Carrier Proteins
Chickens
Cytoskeletal Proteins
Cytoskeleton
Endocytosis
Humans
Intracellular Signaling Peptides and Proteins
Microfilament Proteins
Molecular Sequence Data
Protein Binding
Proteins
Sequence Homology, Amino Acid

Chemicals

Actins
Adaptor Proteins, Signal Transducing
CD2-associated protein
Carrier Proteins
Cytoskeletal Proteins
Intracellular Signaling Peptides and Proteins
Microfilament Proteins
PLEKHO1 protein, human
Proteins

Word Cloud

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