論文 - 詳細
| RRC ID | 45557 |
|---|---|
| 著者 | Edwards SL, Morrison LM, Yorks RM, Hoover CM, Boominathan S, Miller KG. |
| タイトル | UNC-16 (JIP3) Acts Through Synapse-Assembly Proteins to Inhibit the Active Transport of Cell Soma Organelles to Caenorhabditis elegans Motor Neuron Axons. |
| ジャーナル | Genetics |
| Abstract |
The conserved protein UNC-16 (JIP3) inhibits the active transport of some cell soma organelles, such as lysosomes, early endosomes, and Golgi, to the synaptic region of axons. However, little is known about UNC-16's organelle transport regulatory function, which is distinct from its Kinesin-1 adaptor function. We used an unc-16 suppressor screen in Caenorhabditis elegans to discover that UNC-16 acts through CDK-5 (Cdk5) and two conserved synapse assembly proteins: SAD-1 (SAD-A Kinase), and SYD-2 (Liprin-α). Genetic analysis of all combinations of double and triple mutants in unc-16(+) and unc-16(-) backgrounds showed that the three proteins (CDK-5, SAD-1, and SYD-2) are all part of the same organelle transport regulatory system, which we named the CSS system based on its founder proteins. Further genetic analysis revealed roles for SYD-1 (another synapse assembly protein) and STRADα (a SAD-1-interacting protein) in the CSS system. In an unc-16(-) background, loss of the CSS system improved the sluggish locomotion of unc-16 mutants, inhibited axonal lysosome accumulation, and led to the dynein-dependent accumulation of lysosomes in dendrites. Time-lapse imaging of lysosomes in CSS system mutants in unc-16(+) and unc-16(-) backgrounds revealed active transport defects consistent with the steady-state distributions of lysosomes. UNC-16 also uses the CSS system to regulate the distribution of early endosomes in neurons and, to a lesser extent, Golgi. The data reveal a new and unprecedented role for synapse assembly proteins, acting as part of the newly defined CSS system, in mediating UNC-16's organelle transport regulatory function. |
| 巻・号 | 201(1) |
| ページ | 117-41 |
| 公開日 | 2015-9-1 |
| DOI | 10.1534/genetics.115.177345 |
| PII | 201/1/117 |
| PMID | 26354976 |
| PMC | PMC4566257 |
| MeSH | Adaptor Proteins, Signal Transducing / genetics Adaptor Proteins, Signal Transducing / metabolism* Animals Axons / metabolism Biological Transport, Active Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Cyclin-Dependent Kinase 5 / metabolism Intercellular Signaling Peptides and Proteins Intracellular Signaling Peptides and Proteins / metabolism* Motor Neurons / metabolism* Organelles / metabolism* Phosphoproteins / metabolism* Protein Serine-Threonine Kinases / metabolism* |
| IF | 4.015 |
| 引用数 | 13 |
| WOS 分野 | GENETICS & HEREDITY |
| 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 | 6 |
| 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 | tm2175 tm6234 |