GPR39-1b, the 5-transmembrane isoform of GPR39 interacts with neurotensin receptor NTSR1 and modifies its function. (August 2014)

• Record Type: Journal Article
• Authors: Yasuda, Shin-ichiro; Ishida, Junji
• Is Part Of: Journal of receptor and signal transduction research. Volume 34:Number 4(2014)
• Page Start: 307
• Page End: 312
• Publication Date: 2014-08
• Subjects: Cell receptors -- Periodicals; Cellular signal transduction -- Periodicals; 571.6
• DOI: 10.3109/10799893.2014.885050
• Languages: English
• ISSNs: 1079-9893

Abstract

<abstract> <title>Abstract</title> <p>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<sup>2+</sup>, 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<sup>2+</sup> stimulation in calcium mobilization assays, suggesting that GPR39-1b is not a functional receptor of Zn<sup>2+</sup>. To understand the signaling interaction of GPR39-1b, we investigated the dimerization between the isoforms, and conducted bioluminescence resonance energy transfer (BRET<sup>2</sup>) 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<sup>2</sup> 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.</p> </abstract>