GPR39-1b, the 5-transmembrane isoform of GPR39 interacts with neurotensin receptor NTSR1 and modifies its function

AbstractG-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 Zn2+, 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 Zn2+ stimulation in calcium mobilization assays, suggesting that GPR39-1b is not a functional receptor of Zn2+. To understand the signaling interaction of GPR39-1b, we investigated the dimerization between the isoforms, and conducted bioluminescence resonance energy transfer (BRET2) 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 m...