title: Quantitative peptidomics of Purkinje cell degeneration mice.
abstract: Cytosolic carboxypeptidase 1 (CCP1) is a metallopeptidase that removes C-terminal and side-chain glutamates from tubulin. The Purkinje cell degeneration (pcd) mouse lacks CCP1 due to a mutation. Previously, elevated levels of peptides derived from cytosolic and mitochondrial proteins were found in adult pcd mouse brain, raising the possibility that CCP1 functions in the degradation of intracellular peptides. To test this hypothesis, we used a quantitative peptidomics technique to compare peptide levels in wild-type and pcd mice, examining adult heart, spleen, and brain, and presymptomatic 3 week-old amygdala and cerebellum. Contrary to adult mouse brain, young pcd brain and adult heart and spleen did not show a large increase in levels of intracellular peptides. Unexpectedly, levels of peptides derived from secretory pathway proteins were altered in adult pcd mouse brain. The pattern of changes for the intracellular and secretory pathway peptides in pcd mice was generally similar to the pattern observed in mice lacking primary cilia. Collectively, these results suggest that intracellular peptide accumulation in adult pcd mouse brain is a secondary effect and is not due to a role of CCP1 in peptide turnover.
authors.affiliation: Department of Neuroscience, Albert Einstein College of Medicine, Bronx, New York, United States of America.
authors.forename: Iryna
authors.initials: I
authors.lastname: Berezniuk
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Sironi
authors.forename: Jonathan
authors.initials: J
authors.lastname: Wardman
authors.forename: Raymond C
authors.initials: RC
authors.lastname: Pasek
authors.forename: Nicolas F
authors.initials: NF
authors.lastname: Berbari
authors.forename: Bradley K
authors.initials: BK
authors.lastname: Yoder
authors.forename: Lloyd D
authors.initials: LD
authors.lastname: Fricker
mesh_terms: D000595:Amino Acid Sequence; D000679:Amygdala / Q000378:metabolism; D000818:Animals; D002531:Cerebellum / Q000378:metabolism; D005260:Female; D019204:GTP-Binding Proteins / Q000172:deficiency / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism*; D040901:Proteomics; D011689:Purkinje Cells / Q000378:metabolism / Q000473:pathology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D046929:Serine-Type D-Ala-D-Ala Carboxypeptidase / Q000172:deficiency / Q000235:genetics
chemical_list: D010446:Peptide Fragments; D012333:RNA, Messenger; D046929:Serine-Type D-Ala-D-Ala Carboxypeptidase; C420042:Agtpbp1 protein, mouse; D019204:GTP-Binding Proteins