The α_1D-adrenergic receptor (AR) is a key regulator of cardiovascular function, which increases blood pressure and promotes vascular remodeling following activation by the stress hormones norepinephrine and epinephrine. Information on this important G-protein coupled receptor (GPCR) is scant because following transfection into cell culture, the α _1D-AR is retained intracellularly in a non-functional state. Here we report that the α_1D-AR forms a functional signalosome with the dystrophin associated protein complex (DAPC). In this complex, α-, β ₁- and β₂-syntrophin rescue functional expression of the α_1D-AR by localizing it to the plasma membrane, increasing drug binding site formation and downstream signaling responses. We found that α/β ₂-syntrophin double knock-out (KO) mice are significantly hypotensive and are insensitive to α_1D-AR drugs, highlighting that syntrophins are required for α_1D-AR function both in vitro and in vivo. To examine the mechanism by which the DAPC imparts functionality on the α_1D-AR, we performed an extensive proteomics screen with each member of the α_1D-AR signalosome. Our proteomic data discovered two novel members to the α_1D-AR signalosome, α-catulin and α-liprin. Using biochemical and pharmacological techniques, we show that α-catulin binds directly to α-dystrobrevin-1, recruiting phospholipase C isoform β, and ultimately augmenting α_1D-AR coupling to downstream signaling responses. Together these findings show that the DAPC imparts functionality on the α_1D-AR by scaffolding the receptor into discrete microdomains with essential signaling molecules, allowing for both temporal and spatial control of signaling responses.