Regulation of subcellular localization of alpha(1)-adrenoceptor subtypes

alpha (1)-Adrenergic receptors (AR) are members of the superfamily of G pro tein-coupled receptors (GPCRs) which mediate the effects of the sympathetic nervous system. alpha (1)-AR comprise a heterogeneous family of three dist inct isoforms of alpha (1A), or alpha (1B) and alpha (1D); however, very li ttle is known about their difference in physiological role or regulation. W e have recently observed a subtype-specific differences in subcellular loca lization of alpha (1)-ARs; thus, alpha (1A)-AR predominantly localize intra cellularly, while alpha (1B)-AR on the cell surface. To examine the molecul ar mechanism for the subtype-specific differences in subcellular localizati on, we conducted a search for novel proteins that interact with the alpha ( 1B)-AR, specifically focusing on the carboxyl-terminal cytoplasmic domain. Using interaction cloning and biochemical techniques, we demonstrate that g C1q-R interacts with alpha (1B)-AR in vitro and in vivo through the specifi c site, and that in cells which co-express alpha (1B)-AR and gC1q-R, the su bcellular localization of alpha (1B)-AR is markedly altered and its express ion is down-regulated. These results suggest that gC1q-R plays a role in th e regulation of the subcellular localization as well as the function of alp ha (1B)-ARs. (C) 2001 Elsevier Science Inc. All rights reserved.