Identification of CAP as a costameric protein that interacts with filamin C

Mei Zhang, Jun D Liu, Alan Cheng, Stephanie M. DeYoung, Alan R. Saltiel

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Cb1-associated protein (CAP) is an adaptor protein that interacts with both signaling and cytoskeletal proteins. Here, we characterize the expression, localization and potential function of CAP in striated muscle. CAP is markedly induced during myoblast differentiation, and colocalizes with vinculin during costamerogenesis. In adult mice, CAP is enriched in oxidative muscle fibers, and it is found in membrane anchorage complexes, including intercalated discs, costameres, and myotendinous junctions. Using both yeast two-hybrid and proteomic approaches, we identified the sarcomeric protein filamin C (FLNc) as a binding partner for CAP. When overexpressed, CAP recruits FLNc to cell-extracellular matrix adhesions, where the two proteins cooperatively regulate actin reorganization. Moreover, overexpression of CAP inhibits FLNc-induced cell spreading on fibronectin. In dystrophin-deficient mdx mice, the expression and membrane localization of CAP is increased, concomitant with the elevated plasma membrane content of FLNc, suggesting that CAP may compensate for the reduced membrane linkage of the myofibrils due to the loss of the dystroglycan-sarcoglycan complex in these mice. Thus, through its interaction with FLNc, CAP provides another link between the myofibril cytoskeleton and the plasma membrane of muscle cells, and it may play a dynamic role in the regulation and maintenance of muscle structural integrity.

Original languageEnglish (US)
Pages (from-to)4731-4740
Number of pages10
JournalMolecular Biology of the Cell
Volume18
Issue number12
DOIs
StatePublished - Dec 2007
Externally publishedYes

Fingerprint

Filamins
Proteins
Myofibrils
Membranes
Costameres
Sarcoglycans
Cell Membrane
Dystroglycans
Cell-Matrix Junctions
Inbred mdx Mouse
Vinculin
Muscles
Dystrophin
Cytoskeletal Proteins
Striated Muscle
Myoblasts
Protein C
Cytoskeleton
Fibronectins
Proteomics

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Identification of CAP as a costameric protein that interacts with filamin C. / Zhang, Mei; Liu, Jun D; Cheng, Alan; DeYoung, Stephanie M.; Saltiel, Alan R.

In: Molecular Biology of the Cell, Vol. 18, No. 12, 12.2007, p. 4731-4740.

Research output: Contribution to journalArticle

Zhang, Mei ; Liu, Jun D ; Cheng, Alan ; DeYoung, Stephanie M. ; Saltiel, Alan R. / Identification of CAP as a costameric protein that interacts with filamin C. In: Molecular Biology of the Cell. 2007 ; Vol. 18, No. 12. pp. 4731-4740.
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