論文 - 詳細
| RRC ID | 51470 |
|---|---|
| 著者 | Zheng C, Diaz-Cuadros M, Nguyen KCQ, Hall DH, Chalfie M. |
| タイトル | Distinct effects of tubulin isotype mutations on neurite growth in Caenorhabditis elegans. |
| ジャーナル | Mol Biol Cell |
| Abstract |
Tubulins, the building block of microtubules (MTs), play a critical role in both supporting and regulating neurite growth. Eukaryotic genomes contain multiple tubulin isotypes, and their missense mutations cause a range of neurodevelopmental defects. Using the Caenorhabditis elegans touch receptor neurons, we analyzed the effects of 67 tubulin missense mutations on neurite growth. Three types of mutations emerged: 1) loss-of-function mutations, which cause mild defects in neurite growth; 2) antimorphic mutations, which map to the GTP binding site and intradimer and interdimer interfaces, significantly reduce MT stability, and cause severe neurite growth defects; and 3) neomorphic mutations, which map to the exterior surface, increase MT stability, and cause ectopic neurite growth. Structure-function analysis reveals a causal relationship between tubulin structure and MT stability. This stability affects neuronal morphogenesis. As part of this analysis, we engineered several disease-associated human tubulin mutations into C. elegans genes and examined their impact on neuronal development at the cellular level. We also discovered an α-tubulin (TBA-7) that appears to destabilize MTs. Loss of TBA-7 led to the formation of hyperstable MTs and the generation of ectopic neurites; the lack of potential sites for polyamination and polyglutamination on TBA-7 may be responsible for this destabilization. |
| 巻・号 | 28(21) |
| ページ | 2786-2801 |
| 公開日 | 2017-10-15 |
| DOI | 10.1091/mbc.E17-06-0424 |
| PII | mbc.E17-06-0424 |
| PMID | 28835377 |
| PMC | PMC5638583 |
| MeSH | Amino Acid Sequence Animals Caenorhabditis elegans / growth & development* Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / chemistry Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism Humans Microtubules / genetics Microtubules / physiology Mutation Neurites / metabolism* Neurites / physiology* Neurogenesis Neurons / metabolism Protein Isoforms / genetics Tubulin / chemistry Tubulin / genetics* Tubulin / metabolism* |
| IF | 3.791 |
| 引用数 | 7 |
| 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 | tm2143 tm5083 |