CCP1/Nna1 functions in protein turnover in mouse brain: Implications for cell death in Purkinje cell degeneration mice

Author(s)

Berezniuk, Iryna ^[1] ; Sironi, Juan ^[2] ; Callaway, Myrasol B. ^[2] ; Castro, Leandro M. ^[3] ; Hirata, Izaura Y. ^[4] ; Ferro, Emer S. ^[3] ; Fricker, Lloyd D. ^{[2, 1]}

Affiliation

^[1] Yeshiva Univ Albert Einstein Coll Med, Dept Neurosci, Bronx, NY 10461 - USA

^[2] Yeshiva Univ Albert Einstein Coll Med, Dept Mol Pharmacol, Bronx, NY 10461 - USA

^[3] Univ Sao Paulo, Dept Cell & Dev Biol, Sao Paulo - Brazil

^[4] Univ Fed Sao Paulo, Dept Biophys, Sao Paulo - Brazil

• Document type: Journal article
• Source: FASEB JOURNAL; v. 24, n. 6, p. 1813-1823, JUN 2010.
• Web of Science Citations: 33

Abstract

Purkinje cell degeneration (pcd) mice have a mutation within the gene encoding cytosolic carboxypeptidase 1 (CCP1/Nna1), which has homology to metallocarboxypeptidases. To assess the function of CCP1/Nna1, quantitative proteomics and peptidomics approaches were used to compare proteins and peptides in mutant and wild-type mice. Hundreds of peptides derived from cytosolic and mitochondrial proteins are greatly elevated in pcd mouse hypothalamus, amygdala, cortex, prefrontal cortex, and striatum. However, the major proteins detected on 2-D gel electrophoresis were present in mutant and wild-type mouse cortex and hypothalamus at comparable levels, and proteasome activity is normal in these brain regions of pcd mice, suggesting that the increase in cellular peptide levels in the pcd mice is due to reduced degradation of the peptides downstream of the proteasome. Both nondegenerating and degenerating regions of pcd mouse brain, but not wild-type mouse brain, show elevated autophagy, which can be triggered by a decrease in amino acid levels. Taken together with previous studies on CCP1/Nna1, these data suggest that CCP1/Nna1 plays a role in protein turnover by cleaving proteasome-generated peptides into amino acids and that decreased peptide turnover in the pcd mice leads to cell death.-Berezniuk, I., Sironi, J., Callaway, M. B., Castro, L. M., Hirata, I. Y., Ferro, E. S., Fricker, L. D. CCP1/Nna1 functions in protein turnover in mouse brain: Implications for cell death in Purkinje cell degeneration mice. FASEB J. 24, 1813-1823 (2010). www.fasebj.org (AU)

• FAPESP's process: 04/04933-2 - Molecular cell biology of oligopeptidases
• Grantee: Emer Suavinho Ferro
• Support Opportunities: Research Projects - Thematic Grants