Structural Organization and Chromosomal Localization of Three Human Galanin Receptor Genes

Abstract

Human galanin receptor subtypes GALR1, GALR2, and GALR3 are encoded by separate genes that are located on human chromosomes 18q23, 17q25.3, and 22q13.1, respectively. The exon:intron organization of the gene encoding GALR2 (GALNR2) and GALR3 (GALNR3) is conserved, with exon 1 encoding the NH2-terminus to the end of transmembrane domain 3 and exon 2 encoding the remainder of the receptor, from the second intracellular loop to the COOH-terminus. This conservation of structural organization is indicative of a common evolutionary origin for GALNR2 and GALNR3. The exon:intron organization of the gene encoding GALR1 (GALNR1) is different from that of GALNR2 and GALNR3, with exon 1 encoding the NH2-terminus to the end of transmembrane domain 5, exon 2 encoding the third intracellular loop, and exon 3 encoding the remainder of the receptor, from transmembrane domain 6 to the COOH-terminus. The structural organization of GALNR1 suggests convergent evolution for this gene and represents a structural organization that is unique among genes encoding G-protein-coupled receptors.

Electrophysiological evidence for a hyperpolarizing, galanin (1-15)-selective receptor on hippocampal CA3 pyramidal neurons

“…Expression of mRNAs of both GALR1 and GALR2 in LC neurons has been reported (11,26). In contrast to the results in the hippocampus, GAL (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16) and GAL(1-29) affected all tested LC neurons, whereas GAL(1-15) caused a hyperpolarization in 31 of 36 tested neurons and had the weakest effect among the tested peptides. These data show that the GALR or GALRs present in LC neurons bind GAL(1-29) with a higher affinity than GAL (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15) and that some LC neurons respond only to GAL and GAL(1-16) and not GAL (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)…”

“…Tetrodotoxin (TTX) was from Sigma. GAL (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15), GAL (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16), and GAL were dissolved in ACSF as stock solution (10 Ϫ3 M, calculated on the basis of purity of the peptide) and stored at Ϫ70°C in aliquot vials. Drugs were dissolved in warmed, oxygenated ACSF just before use and applied either via bath perfusion or by turning a three-way valve that switched from ACSF to the test solution.…”

Galanin Receptor 1 Has Anti-proliferative Effects in Oral Squamous Cell Carcinoma

“…GAL-mediated events occur via GALR1 as well as two other galanin receptors, GALR2 and GALR3. The latter receptors are products of two different genes on chromosomes 17q25.3 and 22q13.1, respec-tively (18). Although the role of GALR1 has been well characterized in neuronal cells, the expression of this GPCR in nonneuronal cells is poorly understood.…”

Profile of Galanin in Embryonic Stem Cells and Tissues

“…To date, three human and rodent galanin receptor subtypes have been cloned, namely, GalR1, GalR2 and GalR3 (Branchek, Smith et al 2000). High conservation between species exists among receptors of a given subtype but not between subtypes in an individual species (Howard, Tan et al 1997;Iismaa, Fathi et al 1998;Kolakowski, O'Neill et al 1998). All three galanin receptor subtypes are members of the G protein-coupled receptor superfamily, but the subtypes show substantial differences in their functional coupling and subsequent signaling activities, contributing to the diversity of the possible physiological effects of galanin (Fig.…”