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Distribution of neuroendocrine regulatory peptide-1 and -2, and proteolytic processing of their precursor VGF protein in the rat.

Distribution of neuroendocrine regulatory peptide-1 and -2, and proteolytic processing of their precursor VGF protein in the rat.

Authors :
Mishiro-Sato E
Sasaki K
Matsuo T
Kageyama H
Yamaguchi H
Date Y
Matsubara M
Ishizu T
Yoshizawa-Kumagaye K
Satomi Y
Takao T
Shioda S
Nakazato M
Minamino N
Source :
Journal of neurochemistry [J Neurochem] 2010 Aug; Vol. 114 (4), pp. 1097-106. Date of Electronic Publication: 2010 May 26.
Publication Year :
2010

Abstract

Neuroendocrine regulatory peptide (NERP)-1 and NERP-2 are biologically active peptides recently discovered by peptidomic analysis. NERPs are processed out from the 594-residue VGF protein which contains many prohormone convertase cleavage motifs. VGF-deficient mice exhibit a hypermetabolic and infertile phenotype, for which VGF protein-derived peptides including NERPs are presumably responsible. To provide a solid basis for elucidating physiological roles of NERPs, we investigated rat VGF protein processing by chromatographic and mass spectrometric analysis, and immunoblotting, using antibodies against NERPs and the VGF protein C-terminus (VGF-C). Cellular and tissue distribution of immunoreactive (ir) NERPs were also analyzed in the rat. Both ir-NERP-1 and ir-NERP-2, which occur abundantly in the CNS and pituitary, moderately in the gastrointestinal (GI) tract, were mainly localized in neuronal structures. Major endogenous forms of ir-NERPs in the brain and GI tract were identified as NERP-1, NERP-2, and big NERP-2 (NERP-1 + NERP-2), with NERP-1 and big NERP-2 being predominant. Regarding ir-VGF-C peptides, VGF[588-617], VGF[556-617], and VGF[509-617] were found to be major forms. Immunoblotting with the NERP-2 and VGF-C antibodies revealed processing intermediates of 10-37 kDa. Taken together, we deduce that VGF protein is primarily cleaved at 10 sites through the processing pathway common to the brain and GI tract.

Details

Language :
English
ISSN :
1471-4159
Volume :
114
Issue :
4
Database :
MEDLINE
Journal :
Journal of neurochemistry
Publication Type :
Academic Journal
Accession number :
20524965
Full Text :
https://doi.org/10.1111/j.1471-4159.2010.06827.x