論文 - 詳細
| RRC ID | 45586 |
|---|---|
| 著者 | Kurup N, Yan D, Goncharov A, Jin Y. |
| タイトル | Dynamic microtubules drive circuit rewiring in the absence of neurite remodeling. |
| ジャーナル | Curr Biol |
| Abstract |
A striking neuronal connectivity change in C. elegans involves the coordinated elimination of existing synapses and formation of synapses at new locations, without altering neuronal morphology. Here, we investigate the tripartite interaction between dynamic microtubules (MTs), kinesin-1, and vesicular cargo during this synapse remodeling. We find that a reduction in the dynamic MT population in motor neuron axons, resulting from genetic interaction between loss of function in the conserved MAPKKK dlk-1 and an α-tubulin mutation, specifically blocks synapse remodeling. Using live imaging and pharmacological modulation of the MT cytoskeleton, we show that dynamic MTs are increased at the onset of remodeling and are critical for new synapse formation. DLK-1 acts during synapse remodeling, and its function involves MT catastrophe factors including kinesin-13/KLP-7 and spastin/SPAS-1. Through a forward genetic screen, we identify gain-of-function mutations in kinesin-1 that can compensate for reduced dynamic MTs to promote synaptic vesicle transport during remodeling. Our data provide in vivo evidence supporting the requirement of dynamic MTs for kinesin-1-dependent axonal transport and shed light on the role of the MT cytoskeleton in facilitating neural circuit plasticity. |
| 巻・号 | 25(12) |
| ページ | 1594-605 |
| 公開日 | 2015-6-15 |
| DOI | 10.1016/j.cub.2015.04.061 |
| PII | S0960-9822(15)00547-3 |
| PMID | 26051896 |
| PMC | PMC4470761 |
| MeSH | Animals Caenorhabditis elegans / cytology* Caenorhabditis elegans / genetics Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* MAP Kinase Kinase Kinases / genetics MAP Kinase Kinase Kinases / metabolism* Microtubules / metabolism* Mutation Neurites / metabolism* Neuronal Plasticity Synapses / metabolism |
| IF | 9.601 |
| 引用数 | 27 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY |
| 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 | 4 |
| 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 | tm4024 tm2807 tm2143 |