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

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

Author Berezniuk, Iryna Google Scholar
Sironi, Juan Google Scholar
Callaway, Myrasol B. Google Scholar
Castro, Leandro M. Google Scholar
Hirata, Izaura Y. Autor UNIFESP Google Scholar
Ferro, Emer S. Google Scholar
Fricker, Lloyd D. Google Scholar
Institution Yeshiva Univ Albert Einstein Coll Med
Universidade de São Paulo (USP)
Universidade Federal de São Paulo (UNIFESP)
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
Keywords proteasome
carboxypeptidase
aminopeptidase
protein degradation
neurodegeneration
Language English
Sponsor National Institutes of Health
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Financiadora de Estudos e Projetos
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Universidade de Campinas, Campinas, SP, Brazil
Grant number National Institutes of Health: DK-51271
National Institutes of Health: DA-04494
FAPESP: 04/04933-2
FAPESP: 04/14846-0
Financiadora de Estudos e Projetos: A-03/134
Date 2010-06-01
Published in Faseb Journal. Bethesda: Federation Amer Soc Exp Biol, v. 24, n. 6, p. 1813-1823, 2010.
ISSN 0892-6638 (Sherpa/Romeo, impact factor)
Publisher Federation Amer Soc Exp Biol
Extent 1813-1823
Origin http://dx.doi.org/10.1096/fj.09-147942
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000278200000018
URI http://repositorio.unifesp.br/handle/11600/32560

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