PUBLICATION
A family of protein-deglutamylating enzymes associated with neurodegeneration
- Authors
- Rogowski, K., van Dijk, J., Magiera, M.M., Bosc, C., Deloulme, J.C., Bosson, A., Peris, L., Gold, N.D., Lacroix, B., Grau, M.B., Bec, N., Larroque, C., Desagher, S., Holzer, M., Andrieux, A., Moutin, M.J., and Janke, C.
- ID
- ZDB-PUB-110128-8
- Date
- 2010
- Source
- Cell 143(4): 564-578 (Journal)
- Registered Authors
- Keywords
- CELLBIO, MOLNEURO, HUMDISEASE
- MeSH Terms
-
- Amino Acid Sequence
- Animals
- Carboxypeptidases/metabolism*
- Cell Line
- Cell Survival
- Cerebellum/pathology
- GTP-Binding Proteins/metabolism*
- Humans
- Mice
- Mice, Inbred BALB C
- Molecular Sequence Data
- Nerve Degeneration/metabolism*
- Olfactory Bulb/pathology
- Polyglutamic Acid/metabolism*
- Sequence Alignment
- Serine-Type D-Ala-D-Ala Carboxypeptidase/metabolism*
- Tubulin/metabolism
- PubMed
- 21074048 Full text @ Cell
Citation
Rogowski, K., van Dijk, J., Magiera, M.M., Bosc, C., Deloulme, J.C., Bosson, A., Peris, L., Gold, N.D., Lacroix, B., Grau, M.B., Bec, N., Larroque, C., Desagher, S., Holzer, M., Andrieux, A., Moutin, M.J., and Janke, C. (2010) A family of protein-deglutamylating enzymes associated with neurodegeneration. Cell. 143(4):564-578.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping