Alpha-dystrobrevin-1 recruits alpha-catulin to the alpha1D-adrenergic receptor/dystrophin-associated protein complex signalosome

Proc Natl Acad Sci U S A. 2010 Dec 14;107(50):21854-9. doi: 10.1073/pnas.1010819107. Epub 2010 Nov 29.


α(1D)-Adrenergic receptors (ARs) are key regulators of cardiovascular system function that increase blood pressure and promote vascular remodeling. Unfortunately, little information exists about the signaling pathways used by this important G protein-coupled receptor (GPCR). We recently discovered that α(1D)-ARs form a "signalosome" with multiple members of the dystrophin-associated protein complex (DAPC) to become functionally expressed at the plasma membrane and bind ligands. However, the molecular mechanism by which the DAPC imparts functionality to the α(1D)-AR signalosome remains a mystery. To test the hypothesis that previously unidentified molecules are recruited to the α(1D)-AR signalosome, we performed an extensive proteomic analysis on each member of the DAPC. Bioinformatic analysis of our proteomic data sets detected a common interacting protein of relatively unknown function, α-catulin. Coimmunoprecipitation and blot overlay assays indicate that α-catulin is directly recruited to the α(1D)-AR signalosome by the C-terminal domain of α-dystrobrevin-1 and not the closely related splice variant α-dystrobrevin-2. Proteomic and biochemical analysis revealed that α-catulin supersensitizes α(1D)-AR functional responses by recruiting effector molecules to the signalosome. Taken together, our study implicates α-catulin as a unique regulator of GPCR signaling and represents a unique expansion of the intricate and continually evolving array of GPCR signaling networks.

Publication types

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

MeSH terms

  • Dystrophin-Associated Protein Complex / metabolism*
  • Dystrophin-Associated Proteins / genetics
  • Dystrophin-Associated Proteins / metabolism*
  • GTP-Binding Protein alpha Subunits, Gq-G11 / metabolism
  • HEK293 Cells
  • Humans
  • RNA, Small Interfering / metabolism
  • Receptors, Adrenergic, alpha-1 / genetics
  • Receptors, Adrenergic, alpha-1 / metabolism*
  • Signal Transduction / physiology*
  • alpha Catenin / genetics
  • alpha Catenin / metabolism*


  • Dystrophin-Associated Protein Complex
  • Dystrophin-Associated Proteins
  • RNA, Small Interfering
  • Receptors, Adrenergic, alpha-1
  • alpha Catenin
  • dystrobrevin
  • GTP-Binding Protein alpha Subunits, Gq-G11