A defect in cytosolic carboxypeptidase 1 (Nna1) causes autophagy in Purkinje cell degeneration mouse brain.
Purkinje cell degeneration (pcd) is a mouse mutant which is characterized by postnatal degeneration of selective cell types. The pcd mutation was mapped to a gene encoding a cytosolic carboxypeptidase-like protein (CCP), named CCP1/Nna1. Many neurons in pcd mice show increased levels of autophagy, including cell types which do not undergo neurodegeneration. These brain regions have greatly elevated levels of many intracellular peptides, suggesting that CCP1/Nna1 functions in protein turnover by degrading peptides to amino acids. We propose that the lack of CCP1/Nna1 leads to decreases in cellular levels of amino acids, which leads to elevated autophagy as a protective response to cellular amino acid starvation.
Berezniuk
Iryna
I
Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY, USA.
Fricker
Lloyd D
LD
D000818:Animals; D001343:Autophagy; D019204:GTP-Binding Proteins / Q000378:metabolism*; D051379:Mice; D008818:Mice, Neurologic Mutants; D008954:Models, Biological; D009410:Nerve Degeneration / Q000201:enzymology* / Q000473:pathology*; D011689:Purkinje Cells / Q000201:enzymology* / Q000473:pathology*; D046929:Serine-Type D-Ala-D-Ala Carboxypeptidase / Q000378:metabolism*
D046929:Serine-Type D-Ala-D-Ala Carboxypeptidase; C420042:Agtpbp1 protein, mouse; D019204:GTP-Binding Proteins