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| Item Type: | Article |
|---|---|
| Title: | Identification of tubulin deglutamylase among Caenorhabditis elegans and mammalian cytosolic carboxypeptidases (CCPs) |
| Creators Name: | Kimura, Y., Kurabe, N., Ikegami, K., Tsutsumi, K., Konishi, Y., Kaplan, O.I., Kunitomo, H., Iino, Y., Blacque, O.E. and Setou, M. |
| Abstract: | Tubulin polyglutamylation is a reversible post-translational modification, serving important roles in microtubule (MT)-related processes. Polyglutamylases of the tubulin tyrosine ligase-like (TTLL) family add glutamate moieties to specific tubulin glutamate residues, whereas as yet unknown deglutamylases shorten polyglutamate chains. First we investigated regulatory machinery of tubulin glutamylation in MT-based sensory cilia of the roundworm Caenorhabditis elegans. We found that ciliary MTs were polyglutamylated by a process requiring ttll-4. Conversely, loss of ccpp-6 gene function, which encodes one of two cytosolic carboxypeptidases (CCPs), resulted in elevated levels of ciliary MT polyglutamylation. Consistent with a deglutamylase function for ccpp-6, overexpression of this gene in ciliated cells decreased polyglutamylation signals. Similarly, we confirmed that overexpression of murine CCP5, one of two sequence orthologs of nematode ccpp-6, caused a dramatic loss of MT polyglutamylation in cultured mammalian cells. Finally, using an in vitro assay for tubulin glutamylation, we found that recombinantly expressed Myc-tagged CCP5 exhibited deglutamylase biochemical activities. Together, these data from two evolutionarily divergent systems identify C. elegans CCPP-6 and its mammalian ortholog CCP5 as a tubulin deglutamylase. |
| Keywords: | C. Elegans, Carboxypeptidase, Microtubules, Post-Translational Modification, Tubulin, Cilia, Polyglutamylation, Animals, Mice, Caenorhabditis elegans |
| Source: | Journal of Biological Chemistry |
| ISSN: | 0021-9258 |
| Publisher: | American Society for Biochemistry and Molecular Biology |
| Volume: | 285 |
| Number: | 30 |
| Page Range: | 22936-22941 |
| Date: | 23 July 2010 |
| Official Publication: | https://doi.org/10.1074/jbc.C110.128280 |
| PubMed: | View item in PubMed |
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