Archives

  • 2018-07
  • 2019-04
  • 2019-05
  • 2019-06
  • 2019-07
  • 2019-08
  • 2019-09
  • 2019-10
  • 2019-11
  • 2019-12
  • 2020-01
  • 2020-02
  • 2020-03
  • 2020-04
  • 2020-05
  • 2020-06
  • 2020-07
  • 2020-08
  • 2020-09
  • 2020-10
  • 2020-11
  • 2020-12
  • 2021-01
  • 2021-02
  • 2021-03
  • 2021-04
  • 2021-05
  • 2021-06
  • 2021-07
  • 2021-08
  • 2021-09
  • 2021-10
  • 2021-11
  • 2021-12
  • 2022-01
  • 2022-02
  • 2022-03
  • 2022-04
  • 2022-05
  • br Conflict of interest statement br Acknowledgements br Int

    2022-01-20


    Conflict of interest statement
    Acknowledgements
    Introduction Galanin is a multi-functional neuropeptide that is widely distributed in the neuroendocrine system and peripheral tissues of various species. This 29-amino-acid peptide (30 in humans) is proteolytically processed from its precursor, preprogalanin, along with a signal peptide and a galanin message-associated peptide (GMAP), which is more restricted in distribution and biological activities [8], [27]. In mammals, galanin has been implicated in the modulation of different physiological processes including cognitive functions [30], hormone releases [2], [39], energy metabolism [19], neuronal growth [12], [22], as well as the pathophysiology of Alzheimer’s disease [6], [30] and cancer growth [1], [3]. These disparate activities of galanin are mediated by at least three galanin receptor subtypes (GalR1, GalR2 and GalR3), which all belong to the G protein-coupled receptor (GPCR) superfamily, but vary in physiological effects, tissue distribution and ligand affinities (for reviews, see [4], [18]). The mammalian GalR1 and GalR3 were reported to act through the Gi/o type G proteins, resulting in the inhibition of cAMP synthesis, whereas GalR2 is coupled to multiple signaling pathways including Gi/o, G12/13 and predominantly the Gq/11 proteins that activate the phospholipase C (PLC) and Ca2+-dependent cascade [16], [29], [36]. In non-mammalian species, different forms of preprogalanin transcript resulting from alternative splicing and duplicated genes have been reported in quails and goldfish [15], [35]. Avian galanin was isolated from the chicken intestine and quail oviduct, and was specifically identified as an oviposition inducing factor [20], [25]. The localization of avian galanin and its rhein were reported in the mature quail oviduct, where lumbosacral sympathetic ganglionic neurons innervated the uterine muscle layers and released galanin to evoke uterine contractions [28], [34]. On the other hand, in chicken hypothalamus, up-regulation of galanin immunoreactivity was detected after oviposition in the supraoptic nucleus (SON) neurons co-localizing with arginine vasotocin (AVT), suggesting that galanin is involved in the negative feedback regulation of the avian vasotocin system [14]. Despite the important physiological roles that galanin plays in birds, the identities and functionalities of avian galanin receptors remain largely unknown. In our recent study, we reported the first identification of avian GalR1 and a novel galanin receptor subtype, termed as GalR1-like (GalR1-L), from the cDNA cloning of chicken brain [10]. These two receptors share high degrees of similarity in exon/intron organization and sequence homology and a close phylogenetic relationship, thus suggesting their common origin from an early gene duplication event in the vertebrate evolution. Moreover, identification of the novel GalR1-L subtype in chickens, but not in mammals, implies a greater diversity and complexity of the galanin receptor family in non-mammalian species that remain to be determined.
    Materials and methods
    Results
    Discussion The galanin receptor family was known to have three distinct members, GalR1, GalR2 and GalR3, which have been isolated and characterized only in humans, mice and rats. After our recent identification of the GalR1 and GalR1-like receptors in chickens [10], we herein report the cDNA cloning of another two chicken galanin receptor subtypes namely the GalR2 and a novel GalR2-like receptor. Our results demonstrated that both cGalR2 and cGalR2-L cDNAs encode the functional homologs of mammalian GalR2, which are capable of initiating multiple signaling cascades in responses to the cGal (1–29) and hGALP (1–60) activations. Amino acid sequence alignment (Fig. 1) of cGalR2 and cGalR2-L with the mammalian GalR2 reveals high degrees of homology in the sequence identity and structural feature. The cGalR2 cDNA encodes a putative receptor of 371 amino acids, which contains the typical structure of seven-transmembrane helical bundle in the class A, rhodopsin-like GPCR. This receptor shares high overall sequence identities of 65% to 67% with its mammalian GalR2 orthologs, and significantly lower identities with the GalR1 (32–33%), GalR3 (43–45%) and chicken GalR1-L (33%). Amino acid residues in the seven TM helices, the first and second extracellular loops, and the second intracellular loop of chicken GalR2 are highly conserved to those in the mammalian GalR2, whereas sequences of the N- and C-terminal domains are lesser conserved. On the other hand, the cGalR2-L cDNA encodes a novel receptor of 370 amino acids with the peptide length and seven-TM structure that are similar to cGalR2. Among the identified galanin receptor subtypes, cGalR2-L shares the highest amino acid sequence identities with GalR2 of mammals (53–55%) and chickens (59%), and relatively lower sequence identities with the other galanin receptor subtypes (GalR1, 35%; GalR3, 46% to 48%; and cGalR1-L, 37%). Significant sequence divergences between cGalR2 and cGalR2-L are shown in their second and third extracellular loops and the two terminal domains.