Syntrophins regulate alpha 1D‐adrenergic receptor function

Adrenergic receptors (AR) belong to the superfamily of G‐protein coupled receptors (GPCRs). The ARs are divided into three families of receptors: α 1 , α 2 , and β. The α 1 family is comprised of three distinct receptors (α 1A , α 1B and α 1D ) which are important regulators of cardiovascular system function. The α 1 AR family, along with other GPCR families, is believed to function as a multimeric protein complex composed of multiple accessory proteins. These proteins are key regulators of the functional properties of α 1 ‐ARs. To identify new α 1D ‐AR binding partners, the α 1D C‐terminus was used as bait in a yeast 2‐hybrid screen, and α 1 ‐syntrophin was identified. Syntrophins are important scaffolding proteins composed of five isotypes (α 1 , β 1 , β 2 , γ 1 and γ 2 ) which contain a PDZ, two PH and a syntrophin unique domain. To determine the functional importance of this interaction, we have examined the effects of α 1 , β 1 and β 2 syntrophin on α 1D expression and signaling in heterologous cell lines. In addition, tandem affinity purification (TAP) was used with α 1 ‐syntrophin as bait to identify novel proteins scaffolded by syntrophin to α 1D ‐AR. Through this method, more than 1000 new proteins have been identified that can associate with α 1 ‐syntrophin. Future studies will determine the role of syntrophin binding partners on α 1D ‐AR function. Funded by the American Heart Association.