Altered neuropeptide processing in prefrontal cortex of Cpe fat/fat mice: Implications for neuropeptide discovery

Jihyeon Lim, Iryna Berezniuk, Fa Yun Che, Rishi Parikh, Reeta Biswas, Hui Pan, Lloyd D. Fricker

Research output: Contribution to journalArticle

43 Scopus citations

Abstract

The biosynthesis of most neuropeptides and peptide hormones requires a carboxypeptidase such as carboxypeptidase E, which is inactive in Cpe fat/fat mice due to a naturally occurring point mutation. To assess the role of carboxypeptidase E in the processing of peptides in the prefrontal cortex, we used a quantitative peptidomics approach to examine the relative levels of peptides in Cpefat/fat versus wild-type mice. Peptides representing internal fragments of prohormones and other secretory pathway proteins were decreased two- to 10-fold in the Cpefat/fat mouse prefrontal cortex compared with wild-type tissue. Degradation fragments of cytosolic proteins showed no major differences between Cpefat/fat and wild-type mice. Based on this observation, a search strategy for neuropeptides was performed by screening for peptides that decreased in the Cpe fat/fat mouse. Altogether, 32 peptides were identified, of which seven have not been previously reported. The novel peptides include fragments of VGFq4, procholecystokinin and prohormone convertase 2. Interestingly, several of the peptides do not fit with the consensus sites for prohormone convertase 1 and 2, raising the possibility that another endopeptidase is involved with their biosynthesis. Taken together, these findings support the proposal that carboxypeptidase E is the major, but not the only, peptide-processing carboxypeptidase and also demonstrate the feasibility of searching for novel peptides based on their decrease in Cpefat/fat mice.

Original languageEnglish (US)
Pages (from-to)1169-1181
Number of pages13
JournalJournal of Neurochemistry
Volume96
Issue number4
DOIs
StatePublished - Feb 1 2006

Keywords

  • Carboxypeptidase
  • Cholecystokinin
  • Peptide processing
  • Peptidomics
  • Prohormone convertase
  • VGF

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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