Identification of a Novel Inhibitory Actin-Capping Protein Binding Motif in CD2-associated Protein

J Biol Chem. 2006 Jul 14;281(28):19196-203. doi: 10.1074/jbc.M600166200. Epub 2006 May 16.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

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

Substances

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