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A family of protein-deglutamylating enzymes associated with neurodegeneration.
- Source :
-
Cell [Cell] 2010 Nov 12; Vol. 143 (4), pp. 564-78. - Publication Year :
- 2010
-
Abstract
- Polyglutamylation is a posttranslational modification that generates glutamate side chains on tubulins and other proteins. Although this modification has been shown to be reversible, little is known about the enzymes catalyzing deglutamylation. Here we describe the enzymatic mechanism of protein deglutamylation by members of the cytosolic carboxypeptidase (CCP) family. Three enzymes (CCP1, CCP4, and CCP6) catalyze the shortening of polyglutamate chains and a fourth (CCP5) specifically removes the branching point glutamates. In addition, CCP1, CCP4, and CCP6 also remove gene-encoded glutamates from the carboxyl termini of proteins. Accordingly, we show that these enzymes convert detyrosinated tubulin into Δ2-tubulin and also modify other substrates, including myosin light chain kinase 1. We further analyze Purkinje cell degeneration (pcd) mice that lack functional CCP1 and show that microtubule hyperglutamylation is directly linked to neurodegeneration. Taken together, our results reveal that controlling the length of the polyglutamate side chains on tubulin is critical for neuronal survival.<br /> (Copyright © 2010 Elsevier Inc. All rights reserved.)
- Subjects :
- Amino Acid Sequence
Animals
Cell Line
Cell Survival
Cerebellum pathology
Humans
Mice
Mice, Inbred BALB C
Molecular Sequence Data
Olfactory Bulb pathology
Sequence Alignment
Tubulin metabolism
Carboxypeptidases metabolism
GTP-Binding Proteins metabolism
Nerve Degeneration metabolism
Polyglutamic Acid metabolism
Serine-Type D-Ala-D-Ala Carboxypeptidase metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1097-4172
- Volume :
- 143
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Cell
- Publication Type :
- Academic Journal
- Accession number :
- 21074048
- Full Text :
- https://doi.org/10.1016/j.cell.2010.10.014