| Full text | |
| Author(s): |
Wardman, Jonathan H.
[1]
;
Zhang, Xin
[1]
;
Gagnon, Sandra
[2, 3]
;
Castro, Leandro M.
[4]
;
Zhu, Xiaorong
[5]
;
Steiner, Donald F.
[5]
;
Day, Robert
[2, 3]
;
Fricker, Lloyd D.
[1]
Total Authors: 8
|
| Affiliation: | [1] Albert Einstein Coll Med, Dept Mol Pharmacol, Bronx, NY 10461 - USA
[2] Inst Pharmacol Sherbrooke, Sherbrooke, PQ - Canada
[3] Fac Med & Sci La Sante, Sherbrooke, PQ - Canada
[4] Univ Sao Paulo, Dept Cell Biol & Dev, Sao Paulo - Brazil
[5] Univ Chicago, Dept Med, Chicago, IL 60637 - USA
Total Affiliations: 5
|
| Document type: | Journal article |
| Source: | Journal of Neurochemistry; v. 114, n. 1, p. 215-225, JUL 2010. |
| Web of Science Citations: | 47 |
| Abstract | |
P>Neuropeptides are produced from larger precursors by limited proteolysis, first by endopeptidases and then by carboxypeptidases. Major endopeptidases required for these cleavages include prohormone convertase (PC) 1/3 and PC2. In this study, quantitative peptidomics analysis was used to characterize the specific role PC1/3 plays in this process. Peptides isolated from hypothalamus, amygdala, and striatum of PC1/3 null mice were compared with those from heterozygous and wild-type mice. Extracts were labeled with stable isotopic tags and fractionated by HPLC, after which relative peptide levels were determined using tandem mass spectrometry. In total, 92 peptides were found, of which 35 were known neuropeptides or related peptides derived from 15 distinct secretory pathway proteins: 7B2, chromogranin A and B, cocaine- and amphetamine-regulated transcript, procholecystokinin, proenkephalin, promelanin concentrating hormone, proneurotensin, propituitary adenylate cyclase-activating peptide, proSAAS, prosomatosatin, provasoactive intestinal peptide, provasopressin, secretogranin III, and VGF. Among the peptides derived from these proteins, similar to 1/3 were decreased in the PC1/3 null mice relative to wild-type mice, similar to 1/3 showed no change, and similar to 1/3 increased in PC1/3 null. Cleavage sites were analyzed in peptides that showed no change or that decreased in PC1/3 mice, and these results were compared with peptides that showed no change or decreased in previous peptidomic studies with PC2 null mice. Analysis of these sites showed that while PC1/3 and PC2 have overlapping substrate preferences, there are particular cleavage site residues that distinguish peptides preferred by each PC. (AU) | |
| FAPESP's process: | 04/04933-2 - Molecular cell biology of oligopeptidases |
| Grantee: | Emer Suavinho Ferro |
| Support Opportunities: | Research Projects - Thematic Grants |