GPR39 Splice Variants Versus Antisense Gene LYPD1: Expression and Regulation in Gastrointestinal Tract, Endocrine Pancreas, Liver, and White Adipose Tissue

Abstract

G protein-coupled receptor 39 (GPR39) is a constitutively active, orphan member of the ghrelin receptor family that is activated by zinc ions. GPR39 is here described to be expressed in a full-length, biologically active seven-transmembrane form, GPR39-1a, as well as in a truncated splice variant five-transmembrane form, GPR39-1b. The 3' exon of the GPR39 gene overlaps with an antisense gene called LYPD1 (Ly-6/PLAUR domain containing 1). Quantitative RT-PCR analysis demonstrated that GPR39-1a is expressed selectively throughout the gastrointestinal tract, including the liver and pancreas as well as in the kidney and adipose tissue, whereas the truncated GPR39-1b form has a more broad expression pattern, including the central nervous system but with highest expression in the stomach and small intestine. In contrast, the LYPD1 antisense gene is highly expressed throughout the central nervous system as characterized with both quantitative RT-PCR and in situ hybridization analysis. A functional analysis of the GPR39 promoter region identified sites for the hepatocyte nuclear factors 1alpha and 4alpha (HNF-1alpha and -4alpha) and specificity protein 1 (SP1) transcription factors as being important for the expression of GPR39. In vivo experiments in rats demonstrated that GPR39 is up-regulated in adipose tissue during fasting and in response to streptozotocin treatment, although its expression is kept constant in the liver from the same animals. GPR39-1a was expressed in white but not brown adipose tissue and was down-regulated during adipocyte differentiation of fibroblasts. It is concluded that the transcriptional control mechanism, the tissue expression pattern, and in vivo response to physiological stimuli all indicate that the GPR39 receptor very likely is of importance for the function of a number of metabolic organs, including the liver, gastrointestinal tract, pancreas, and adipose tissue.

Two alternatively spliced GPR39 transcripts in seabream: molecular cloning, genomic organization, and regulation of gene expression by metabolic signals

“…However, sbGPR39-1b is also expressed in other tissues where there is little sbGPR39-1a, particularly in the brain regions including the hypothalamus and pituitary. A similar tissue expression pattern of GPR39-1b in mouse was reported by Egerod et al (2007). This conserved GPR39-1b expression pattern in mammals and fish implies a possible physiological role of the truncated receptor in these tissues.…”

“…In the present study, we have clearly demonstrated the presence of two alternatively spliced forms of GPR39 in teleosts as well as in mammals, and that these two receptors in seabream are distinct in biological function and are differentially expressed. During the preparation of this manuscript, Egerod et al (2007) also reported that GPR39-1b transcripts are found in human, mouse, rat, and chicken, further supporting the notion that the presence of two GPR39 transcripts is a general phenomenon among vertebrates.…”

Obestatin prevents analgesic tolerance to morphine and reverses the effects of mild morphine withdrawal in mice

“…GPR39 receptor has two splice variants, GPR39-1a and GPR39-1b. GPR39-1a is expressed selectively in the gastrointestinal tract, whereas GPR39-1b has a wider expression pattern, including nuclei in the central nervous system, for example the amygdala, and hippocampus [4]. Later studies reported that GPR39 may not have obestatin as a main ligand [5][6][7].…”

cDNA Cloning and mRNA Expression of Bovine GPR39

“…GPR39 mRNA has been shown to be expressed in a wide range of tissues in humans, rats, mice and chickens, with relatively higher levels in the liver, kidney, pancreas and gastrointestinal (GI) tract [3,12,13,19,21]. In GPR39-deficient mice, accelerated gastric emptying of a solid meal, body weight gain and high body fat composition have been observed, which suggests that GPR39 plays important roles in digestive and metabolic functions [13].…”

“…gov/BLAST) showed the presence of an approximately 17.8 kb intron between positions 994 and 995 in the GPR39 cDNA, which indicates that the bovine GPR39 gene consists of 2 exons. Recently, the human GPR39 gene was shown to have a similar exon / intron structure [3].…”