論文 - 詳細
| RRC ID | 34886 |
|---|---|
| 著者 | Pathak T, Agrawal T, Richhariya S, Sadaf S, Hasan G. |
| タイトル | Store-Operated Calcium Entry through Orai Is Required for Transcriptional Maturation of the Flight Circuit in Drosophila. |
| ジャーナル | J Neurosci |
| Abstract |
UNLABELLED:Store operated calcium entry (SOCE) is thought to primarily regulate calcium homeostasis in neurons. Subsequent to identification of Orai as the SOCE channel in nonexcitable cells, investigation of Orai function in neurons demonstrated a requirement for SOCE in Drosophila flight. Here, by analysis of an Orai mutant and by controlled expression of a dominant-negative Drosophila Orai transgene, we show that Orai-mediated SOCE is required in dopaminergic interneurons of the flight circuit during pupal development. Expression of dominant-negative Orai in dopaminergic neurons of pupae abolished flight. The loss of Orai-mediated SOCE alters transcriptional regulation of dopaminergic neurons, leading to downregulation of the enzyme tyrosine hydroxylase, which is essential for dopamine synthesis, and the dopamine transporter, which is required for dopamine uptake after synaptic release. These studies suggest that modulation of SOCE could serve as a novel mechanism for restoring dopamine levels in dopaminergic neurons. SIGNIFICANCE STATEMENT:The specificity of an animal's response to an environmental stimulus is determined in part by the release of neurotransmitters, which are sensed by responding neurons through cognate receptors on their surface. One way by which neurons respond is through release of calcium from intracellular stores followed by store refilling from extracellular calcium sources. This mechanism is called store-operated calcium entry (SOCE). The function of SOCE in neurons has been debated. Here we describe a new function for SOCE in the regulation of neurotransmitter levels in Drosophila flight neurons. This cell-signaling mechanism is required to maintain optimal levels of a key enzyme for dopamine synthesis and may serve as a mechanism for restoring dopamine levels in relevant pathological conditions. |
| 巻・号 | 35(40) |
| ページ | 13784-99 |
| 公開日 | 2015-10-7 |
| DOI | 10.1523/JNEUROSCI.1680-15.2015 |
| PII | 35/40/13784 |
| PMID | 26446229 |
| PMC | PMC6605383 |
| MeSH | Acetyl-CoA Carboxylase / genetics Acetyl-CoA Carboxylase / metabolism Animals Animals, Genetically Modified Calcium / metabolism* Calcium Signaling / genetics Cells, Cultured Dopamine Plasma Membrane Transport Proteins / metabolism Dopaminergic Neurons / metabolism Drosophila Drosophila Proteins / genetics Drosophila Proteins / metabolism* Flight, Animal / physiology* Flow Cytometry Gene Expression Regulation, Developmental / genetics* Larva Membrane Proteins / genetics Membrane Proteins / metabolism* Mutation / genetics* Neural Pathways / physiology ORAI1 Protein Pupa Rats Tyrosine 3-Monooxygenase / metabolism |
| IF | 5.674 |
| 引用数 | 25 |
| WOS 分野 | NEUROSCIENCES |
| リソース情報 | |
| ショウジョウバエ | 1063R-2 |