論文 - 詳細
| RRC ID | 57246 |
|---|---|
| 著者 | Mallik B, Dwivedi MK, Mushtaq Z, Kumari M, Verma PK, Kumar V. |
| タイトル | Regulation of neuromuscular junction organization by Rab2 and its effector ICA69 in Drosophila. |
| ジャーナル | Development |
| Abstract |
The mechanisms underlying synaptic differentiation, which involves neuronal membrane and cytoskeletal remodeling, are not completely understood. We performed a targeted RNAi-mediated screen of Drosophila BAR-domain proteins and identified islet cell autoantigen 69 kDa (ICA69) as one of the key regulators of morphological differentiation of the larval neuromuscular junction (NMJ). We show that Drosophila ICA69 colocalizes with α-Spectrin at the NMJ. The conserved N-BAR domain of ICA69 deforms liposomes in vitro Full-length ICA69 and the ICAC but not the N-BAR domain of ICA69 induce filopodia in cultured cells. Consistent with its cytoskeleton regulatory role, ICA69 mutants show reduced α-Spectrin immunoreactivity at the larval NMJ. Manipulating levels of ICA69 or its interactor PICK1 alters the synaptic level of ionotropic glutamate receptors (iGluRs). Moreover, reducing PICK1 or Rab2 levels phenocopies ICA69 mutation. Interestingly, Rab2 regulates not only synaptic iGluR but also ICA69 levels. Thus, our data suggest that: (1) ICA69 regulates NMJ organization through a pathway that involves PICK1 and Rab2, and (2) Rab2 functions genetically upstream of ICA69 and regulates NMJ organization and targeting/retention of iGluRs by regulating ICA69 levels. |
| 巻・号 | 144(11) |
| ページ | 2032-2044 |
| 公開日 | 2017-6-1 |
| DOI | 10.1242/dev.145920 |
| PII | dev.145920 |
| PMID | 28455372 |
| MeSH | Animals Autoantigens / metabolism* Cells, Cultured Drosophila Proteins / metabolism* Drosophila melanogaster / metabolism* Gene Knockdown Techniques Larva / metabolism Liposomes Mutation / genetics Neuromuscular Junction / metabolism* Protein Subunits / metabolism Protein Transport Pseudopodia / metabolism RNA Interference Receptors, Ionotropic Glutamate / metabolism Synapses / metabolism rab2 GTP-Binding Protein / metabolism* |
| IF | 5.763 |
| 引用数 | 2 |
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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 |
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