Chicken neuropeptide Y-family receptor Y4: a receptor with equal affinity for pancreatic polypeptide, neuropeptide Y and peptide YY

Abstract

Within the neuropeptide Y (NPY) family of peptides, pancreatic polypeptide is the most divergent across species. It differs in 20 of 36 positions between human and chicken. In mammals, it binds primarily to the Y4 receptor, to which NPY and peptide YY (PYY) bind with lower affinities. Because of these large sequence differences in pancreatic polypeptide, we decided to characterise the chicken Y4 receptor. We report here that Y4 displays the least sequence conservation among the Y-family receptors, with only 57-60% overall amino acid identity between chicken and mammals, compared with 64-83% for the Y1, Y2 and Y5 receptors. After expression of the chicken Y4 receptor in COS-7 cells, I-pPYY, chicken pancreatic polypeptide bound with high affinity at 140 pM. Interestingly, chicken PYY bound with even greater affinity at 68 pM. The affinity of NPY, 160 pM, was similar to that of pancreatic polypeptide. Chicken Y4 is less sensitive than is mammalian Y4 to truncation of the amino terminus of the NPY molecule. RT-PCR revealed expression in several peripheral organs, including adipose tissue and oviduct. In brain, Y4 mRNA was detected in the brainstem, cerebellum and hippocampus. In situ hybridisation to brain sections showed expression in the dorsal motor nucleus of the vagus in the brainstem. Thus the chicken Y4 receptor is less selective and anatomically more widespread than that in mammals, probably reflecting the original properties of the Y4 receptor.

Neuropeptide Y family receptors Y1 and Y2 from sea lamprey, Petromyzon marinus

“…The first step is to identify all components of the peptide-receptor system in these species. We have previously identified the full repertoire of NPY-family peptides and receptors in a broad range of species and have performed studies of peptide-receptor preferences especially in mammals, chicken, the western clawed frog Xenopus (Silurana) tropicalis, and zebrafish (Bromee et al, 2006;Fallmar et al, 2011;Holmberg et al, 2002;Larhammar et al, 2001;Lundell et al, 2002;Salaneck et al, 2000;Sundstrom et al, 2013). Each lineage displays some unique partnership features for peptides and receptors.…”

“…Each lineage displays some unique partnership features for peptides and receptors. For instance, in mammals PP and Y4 have a clear preference for each other, and this selectivity is greater in rat (Lundell et al, 1996) than in human, while the chicken Y4 receptor binds to the three native ligands with almost equal affinities (Lundell et al, 2002). In the zebrafish, which has the three peptides NPYa, PYYa and PYYb and the seven receptors Y1, Y2, Y2-2, Y4, Y7, Y8a and Y8b, one of the major differences is that PYYa has lower affinity than the other two peptides for Y2 whose closest relative, the teleost-specific Y2-2 receptor, has very similar affinities for the three peptides (Fallmar et al, 2011).…”

Evolutionary perspective on the NPY-PYY-PP peptides and their receptors

“…If so, Y2 and Y4 may have other roles in fish that remain to be identified. The importance of PYY and PP in appetite inhibition will also be interesting to explore in the chicken where the Y4 receptor binds to both of these ligands [91]. It is possible that appetite inhibition by PYY and PP through Y2 and Y4, respectively, is a more recent function, perhaps evolved in mammals.…”

“…The overall impression is that extensive differences exist across species for individual receptor subtypes. Among the most conspicuous differences to mammals it is worth noting that chicken Y4 mRNA [91] is expressed in liver and spleen, in addition to adipose tissue like in mammals which otherwise have expression mostly in the gastrointestinal tract [130,131]. The shark Y4 receptor mRNA is expressed in brain, retina, kidney and muscle [97] (see Fig.…”

“…Orthologues of all of the mammalian subtypes have been identified in the domestic chicken [89][90][91] (Fredriksson and Larhammar, unpublished). The exciting difference is that chicken has retained the ancient duplicate of Y2, namely the Y7 gene (Bromée, Sjödin and Larhammar, unpublished), which has been lost in mammals.…”