Mexneurin is a novel precursor of peptides in the central nervous system of rodents

• Published in: FEBS letters 2017-06, Vol.591 (12), p.1627-1636
• Main Authors: Matus‐Ortega, Maura E., Leff Gelman, Philippe, Calva‐Nieves, Juan C., Flores‐Zamora, Anabel, Salazar‐Juárez, Alberto, Torner‐Aguilar, Carlos‐Alejandro, Gamba, Gerardo, De Los Heros, Paola, Peng, Bonnie, Pintar, John E., Gompf, Heinrich S., Allen, Charles N., Antón‐Palma, Benito
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Animals; Base Sequence; Brain - cytology; Brain - metabolism; Brain - physiology; endomorphin; Evoked Potentials; Guanosine 5'-O-(3-Thiotriphosphate) - metabolism; Hippocampus - cytology; Hippocampus - metabolism; Hippocampus - physiology; Ligands; Male; Mice, Inbred BALB C; Nerve Tissue Proteins - chemistry; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Neurons - cytology; Neurons - metabolism; Neurons - physiology; Nuclear Proteins - chemistry; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; Open Reading Frames; opioid peptides; Patch-Clamp Techniques; protein precursor; Protein Precursors - chemistry; Protein Precursors - genetics; Protein Precursors - metabolism; Protein Processing, Post-Translational; Proteolysis; Rats, Sprague-Dawley; Rats, Wistar; RNA, Messenger - metabolism; Sequence Analysis, DNA
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1002/1873-3468.12679

Endomorphins (EMs) have been proposed as the endogenous ligand agonists of the μ‐opioid receptor; however, no propeptide precursor protein for EMs has been identified. Here, to identify the presumed precursor of EMs, we designed an immunoscreening assay using specific affinity‐purified rabbit antisera raised against synthetic EMs in a whole‐mouse brain cDNA library. Following this approach, we identify a DNA sequence encoding a protein precursor, which we name proMexneurin, that contains three different peptide sequences: Mexneurin‐1 (an EM‐like peptide), Mexneurin‐2, and Mexneurin‐3, a peptide which appears to be unrelated to EMs. RT‐PCR analysis and in situ hybridization reveal a widespread distribution of proMexneurin mRNA throughout the mouse brain. Both Mexneurin‐1 and Mexneurin‐3 peptides display biological activities in the mouse CNS.