期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2010
卷号：107
期号：50
页码：21854-21859
DOI：10.1073/pnas.1010819107
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：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 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 1D-AR signalosome remains a mystery. To test the hypothesis that previously unidentified molecules are recruited to the 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, -catulin. Coimmunoprecipitation and blot overlay assays indicate that -catulin is directly recruited to the 1D-AR signalosome by the C-terminal domain of -dystrobrevin-1 and not the closely related splice variant -dystrobrevin-2. Proteomic and biochemical analysis revealed that -catulin supersensitizes 1D-AR functional responses by recruiting effector molecules to the signalosome. Taken together, our study implicates -catulin as a unique regulator of GPCR signaling and represents a unique expansion of the intricate and continually evolving array of GPCR signaling networks.
