論文 - 詳細
| RRC ID | 45574 |
|---|---|
| 著者 | Hardaway JA, Sturgeon SM, Snarrenberg CL, Li Z, Xu XZ, Bermingham DP, Odiase P, Spencer WC, Miller DM 3rd, Carvelli L, Hardie SL, Blakely RD. |
| タイトル | Glial Expression of the Caenorhabditis elegans Gene swip-10 Supports Glutamate Dependent Control of Extrasynaptic Dopamine Signaling. |
| ジャーナル | J Neurosci |
| Abstract |
Glial cells play a critical role in shaping neuronal development, structure, and function. In a screen for Caenorhabditis elegans mutants that display dopamine (DA)-dependent, Swimming-Induced Paralysis (Swip), we identified a novel gene, swip-10, the expression of which in glia is required to support normal swimming behavior. swip-10 mutants display reduced locomotion rates on plates, consistent with our findings of elevated rates of presynaptic DA vesicle fusion using fluorescence recovery after photobleaching. In addition, swip-10 mutants exhibit elevated DA neuron excitability upon contact with food, as detected by in vivo Ca(2+) monitoring, that can be rescued by glial expression of swip-10. Mammalian glia exert powerful control of neuronal excitability via transporter-dependent buffering of extracellular glutamate (Glu). Consistent with this idea, swip-10 paralysis was blunted in mutants deficient in either vesicular Glu release or Glu receptor expression and could be phenocopied by mutations that disrupt the function of plasma membrane Glu transporters, most noticeably glt-1, the ortholog of mammalian astrocytic GLT1 (EAAT2). swip-10 encodes a protein containing a highly conserved metallo-β-lactamase domain, within which our swip-10 mutations are located and where engineered mutations disrupt Swip rescue. Sequence alignments identify the CNS-expressed gene MBLAC1 as a putative mammalian ortholog. Together, our studies provide evidence of a novel pathway in glial cells regulated by swip-10 that limits DA neuron excitability, DA secretion, and DA-dependent behaviors through modulation of Glu signaling. |
| 巻・号 | 35(25) |
| ページ | 9409-23 |
| 公開日 | 2015-6-24 |
| DOI | 10.1523/JNEUROSCI.0800-15.2015 |
| PII | 35/25/9409 |
| PMID | 26109664 |
| PMC | PMC4478255 |
| MeSH | Animals Animals, Genetically Modified Caenorhabditis elegans / physiology* Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism* Dopamine / metabolism* Dopamine Plasma Membrane Transport Proteins / genetics Dopamine Plasma Membrane Transport Proteins / metabolism* Glutamic Acid / metabolism Microscopy, Confocal Motor Activity / physiology Nerve Tissue Proteins / genetics Nerve Tissue Proteins / metabolism* Neuroglia / metabolism* Neurons / metabolism Reverse Transcriptase Polymerase Chain Reaction Signal Transduction / physiology* |
| IF | 5.674 |
| 引用数 | 17 |
| WOS 分野 | NEUROSCIENCES |
| 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 | tm2261 tm5915 tm669 tm3506 tm2877 tm3285 tm355 tm1811 tm1766 tm3239 tm2729 tm1316 tm1641 |