論文 - 詳細
| RRC ID | 51516 |
|---|---|
| 著者 | O'Hagan R, Silva M, Nguyen KCQ, Zhang W, Bellotti S, Ramadan YH, Hall DH, Barr MM. |
| タイトル | Glutamylation Regulates Transport, Specializes Function, and Sculpts the Structure of Cilia. |
| ジャーナル | Curr Biol |
| Abstract |
Ciliary microtubules (MTs) are extensively decorated with post-translational modifications (PTMs), such as glutamylation of tubulin tails. PTMs and tubulin isotype diversity act as a "tubulin code" that regulates cytoskeletal stability and the activity of MT-associated proteins such as kinesins. We previously showed that, in C. elegans cilia, the deglutamylase CCPP-1 affects ciliary ultrastructure, localization of the TRP channel PKD-2 and the kinesin-3 KLP-6, and velocity of the kinesin-2 OSM-3/KIF17, whereas a cell-specific α-tubulin isotype regulates ciliary ultrastructure, intraflagellar transport, and ciliary functions of extracellular vesicle (EV)-releasing neurons. Here we examine the role of PTMs and the tubulin code in the ciliary specialization of EV-releasing neurons using genetics, fluorescence microscopy, kymography, electron microscopy, and sensory behavioral assays. Although the C. elegans genome encodes five tubulin tyrosine ligase-like (TTLL) glutamylases, only ttll-11 specifically regulates PKD-2 localization in EV-releasing neurons. In EV-releasing cephalic male (CEM) cilia, TTLL-11 and the deglutamylase CCPP-1 regulate remodeling of 9+0 MT doublets into 18 singlet MTs. Balanced TTLL-11 and CCPP-1 activity fine-tunes glutamylation to control the velocity of the kinesin-2 OSM-3/KIF17 and kinesin-3 KLP-6 without affecting the intraflagellar transport (IFT) kinesin-II. TTLL-11 is transported by ciliary motors. TTLL-11 and CCPP-1 are also required for the ciliary function of releasing bioactive EVs, and TTLL-11 is itself a novel EV cargo. Therefore, MT glutamylation, as part of the tubulin code, controls ciliary specialization, ciliary motor-based transport, and ciliary EV release in a living animal. We suggest that cell-specific control of MT glutamylation may be a conserved mechanism to specialize the form and function of cilia. |
| 巻・号 | 27(22) |
| ページ | 3430-3441.e6 |
| 公開日 | 2017-11-20 |
| DOI | 10.1016/j.cub.2017.09.066 |
| PII | S0960-9822(17)31266-6 |
| PMID | 29129530 |
| PMC | PMC5698134 |
| MeSH | Animals Caenorhabditis elegans / metabolism Caenorhabditis elegans Proteins / metabolism* Carboxypeptidases / metabolism* Cilia / metabolism* Extracellular Vesicles / metabolism Extracellular Vesicles / physiology Microtubules / metabolism Peptide Synthases / genetics Peptide Synthases / metabolism* Protein Processing, Post-Translational Protein Transport / physiology Tubulin / metabolism |
| IF | 9.601 |
| 引用数 | 16 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 15 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| 線虫 | tm324 tm3310 tm3360 tm3389 tm3871 tm3889 tm4059 |