Regulation of subcellular localization of alpha1-adrenoceptor subtypes.
Alpha1-adrenergic receptors (AR) are members of the superfamily of G protein-coupled receptors (GPCRs) which mediate the effects of the sympathetic nervous system. Alpha1-AR comprise a heterogeneous family of three distinct isoforms of alpha1A, alpha1B and alpha1D; however, very little is known about their difference in physiological role or regulation. We have recently observed a subtype-specific differences in subcellular localization of alpha1-ARs; thus, alpha1A-AR predominantly localize intracellularly, while alpha1B-AR on the cell surface. To examine the molecular mechanism for the subtype-specific differences in subcellular localization, we conducted a search for novel proteins that interact with the alpha1B-AR, specifically focusing on the carboxyl-terminal cytoplasmic domain. Using interaction cloning and biochemical techniques, we demonstrate that gC1q-R interacts with alpha1B-AR in vitro and in vivo through the specific site, and that in cells which co-express alpha1B-AR and gC1q-R, the subcellular localization of alpha1B-AR is markedly altered and its expression is down-regulated. These results suggest that gC1q-R plays a role in the regulation of the subcellular localization as well as the function of alpha1B-ARs.
Hirasawa
A
A
Department of Molecular, Cell Pharmacology, National Children's Medical Research Center, Tokyo, Japan.
Awaji
T
T
Xu
Z
Z
Shinoura
H
H
Tsujimoto
G
G
D000818:Animals; D015153:Blotting, Western; D003001:Cloning, Molecular; D006224:Cricetinae; D015536:Down-Regulation / Q000502:physiology; D005434:Flow Cytometry; D049452:Green Fluorescent Proteins; D066298:In Vitro Techniques; D007425:Intracellular Membranes / Q000378:metabolism* / Q000648:ultrastructure; D008164:Luminescent Proteins / Q000378:metabolism; D018613:Microscopy, Confocal; D016297:Mutagenesis, Site-Directed; D011233:Precipitin Tests; D017434:Protein Structure, Tertiary / Q000502:physiology; D051381:Rats; D018340:Receptors, Adrenergic, alpha-1 / Q000145:classification / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism
D008164:Luminescent Proteins; D018340:Receptors, Adrenergic, alpha-1; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins