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

J. Neurochem. (2010) 114, 1097-1106. 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 mi...

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Veröffentlicht in:Journal of neurochemistry 2010-08, Vol.114 (4), p.1097-1106
Hauptverfasser: Mishiro-Sato, Emi, Sasaki, Kazuki, Matsuo, Takashi, Kageyama, Haruaki, Yamaguchi, Hideki, Date, Yukari, Matsubara, Masako, Ishizu, Takehiro, Yoshizawa-Kumagaye, Kumiko, Satomi, Yoshinori, Takao, Toshifumi, Shioda, Seiji, Nakazato, Masamitsu, Minamino, Naoto
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Sprache:eng
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Zusammenfassung:J. Neurochem. (2010) 114, 1097-1106. 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.
ISSN:0022-3042
1471-4159
DOI:10.1111/j.1471-4159.2010.06827.x