title: GPR39-1b, the 5-transmembrane isoform of GPR39 interacts with neurotensin receptor NTSR1 and modifies its function.
abstract: G-protein-coupled receptor 39 (GPR39), a member of the ghrelin receptor family, has a full-length isoform GPR39-1a and a truncated isoform GPR39-1b. While GPR39-1a was clarified as a receptor of Zn(2+), the characteristic property of GPR39-1b remains unknown. Therefore, in this study, the molecular functions of GPR39-1b were explored in cell culture. In contrast to GPR39-1a, GPR39-1b showed no response to Zn(2+) stimulation in calcium mobilization assays, suggesting that GPR39-1b is not a functional receptor of Zn(2+). To understand the signaling interaction of GPR39-1b, we investigated the dimerization between the isoforms, and conducted bioluminescence resonance energy transfer (BRET(2)) assays. The results indicated that GPR39-1b homodimerized, but did not heterodimerize with GPR39-1a. We subsequently attempted to search the heterodimeric counterparts of GPR39-1b. Neurotensin receptor 1 (NTSR1) was also targeted as a GPR39-1b interacting partner because of its highly conserved amino acid sequence and mRNA localization, which was similar to GPR39-1b. BRET(2) assays demonstrated that GPR39-1b heterodimerized with NTSR1. To examine the effect of GPR39-1b on NTRS1-mediated cAMP/PKA signaling, we used the cAMP responsive element-luciferase assays and observed that GPR39-1b attenuated neurotensin-induced NTSR1 signaling. Taken together, our results provided a novel regulatory mechanism for GPR39-1b in NTRS1 signaling.
authors: Pharmacology Research Laboratories II, Mitsubishi Tanabe Pharma Corporation , Kawagishi, Toda-shi, Saitama , Japan and.
authors: Shin-ichiro
authors: S
authors: Yasuda
authors: Junji
authors: J
authors: Ishida
mesh_terms: D060807:Bioluminescence Resonance Energy Transfer Techniques; D002118:Calcium / Q000737:chemistry / Q000378:metabolism*; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D019281:Dimerization; D057809:HEK293 Cells; D006801:Humans; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry / Q000378:metabolism*; D018028:Receptors, Neurotensin / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics*; D015032:Zinc / Q000378:metabolism
chemical_list: C495797:GPR39 protein, human; D020033:Protein Isoforms; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D018028:Receptors, Neurotensin; C114036:neurotensin type 1 receptor; D000242:Cyclic AMP; D015032:Zinc; D002118:Calcium
keywords: BRET; G-protein-coupled receptor; GPR39; NTSR1; heterodimerization; neurotensin