Proglucagons in vertebrates: Expression and processing of multiple genes in a bony fish

In contrast to mammals, where a single proglucagon (PG) gene encodes three peptides: glucagon, glucagon-like peptide 1 and glucagon-like peptide 2 (GLP-1; GLP-2), many non-mammalian vertebrates carry multiple PG genes. Here, we investigate proglucagon mRNA sequences, their tissue expression and proc...

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Bibliographic Details
Published in:Comparative Biochemistry and Physiology Part B: Biochemistry and Molecular Biology 2016-09, Vol.199, p.58-66
Main Authors: Busby, Ellen R., Mommsen, Thomas P.
Format: Article
Language:English
Subjects:
Alternative splicing
Amino Acid Sequence
Animals
Base Sequence
Differential expression
Endocrine pancreas
Fishes - genetics
Fishes - metabolism
Gene Expression Regulation
Intestine
Organ Specificity
Proglucagon
Proglucagon - biosynthesis
Proglucagon - chemistry
Proglucagon - genetics
Proglucagon - metabolism
Protein Transport
RNA, Messenger - genetics
RNA, Messenger - metabolism
Sequence Homology, Nucleic Acid
Teleost
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Summary:In contrast to mammals, where a single proglucagon (PG) gene encodes three peptides: glucagon, glucagon-like peptide 1 and glucagon-like peptide 2 (GLP-1; GLP-2), many non-mammalian vertebrates carry multiple PG genes. Here, we investigate proglucagon mRNA sequences, their tissue expression and processing in a diploid bony fish. Copper rockfish (Sebastes caurinus) express two independent genes coding for distinct proglucagon sequences (PG I, PG II), with PG II lacking the GLP-2 sequence. These genes are differentially transcribed in the endocrine pancreas, the brain, and the gastrointestinal tract. Alternative splicing identified in rockfish is only one part of this complex regulation of the PG transcripts: the system has the potential to produce two glucagons, four GLP-1s and a single GLP-2, or any combination of these peptides. Mass spectrometric analysis of partially purified PG-derived peptides in endocrine pancreas confirms translation of both PG transcripts and differential processing of the resulting peptides. The complex differential regulation of the two PG genes and their continued presence in this extant teleostean fish strongly suggests unique and, as yet largely unidentified, roles for the peptide products encoded in each gene.
ISSN:1096-4959
1879-1107
DOI:10.1016/j.cbpb.2016.02.004