論文 - 詳細
| RRC ID | 3378 |
|---|---|
| 著者 | Espelt MV, Estevez AY, Yin X, Strange K. |
| タイトル | Oscillatory Ca2+ signaling in the isolated Caenorhabditis elegans intestine: role of the inositol-1,4,5-trisphosphate receptor and phospholipases C beta and gamma. |
| ジャーナル | J Gen Physiol |
| Abstract |
Defecation in the nematode Caenorhabditis elegans is a readily observable ultradian behavioral rhythm that occurs once every 45-50 s and is mediated in part by posterior body wall muscle contraction (pBoc). pBoc is not regulated by neural input but instead is likely controlled by rhythmic Ca(2+) oscillations in the intestinal epithelium. We developed an isolated nematode intestine preparation that allows combined physiological, genetic, and molecular characterization of oscillatory Ca(2+) signaling. Isolated intestines loaded with fluo-4 AM exhibit spontaneous rhythmic Ca(2+) oscillations with a period of approximately 50 s. Oscillations were only detected in the apical cell pole of the intestinal epithelium and occur as a posterior-to-anterior moving intercellular Ca(2+) wave. Loss-of-function mutations in the inositol-1,4,5-trisphosphate (IP(3)) receptor ITR-1 reduce pBoc and Ca(2+) oscillation frequency and intercellular Ca(2+) wave velocity. In contrast, gain-of-function mutations in the IP(3) binding and regulatory domains of ITR-1 have no effect on pBoc or Ca(2+) oscillation frequency but dramatically increase the speed of the intercellular Ca(2+) wave. Systemic RNA interference (RNAi) screening of the six C. elegans phospholipase C (PLC)-encoding genes demonstrated that pBoc and Ca(2+) oscillations require the combined function of PLC-gamma and PLC-beta homologues. Disruption of PLC-gamma and PLC-beta activity by mutation or RNAi induced arrhythmia in pBoc and intestinal Ca(2+) oscillations. The function of the two enzymes is additive. Epistasis analysis suggests that PLC-gamma functions primarily to generate IP(3) that controls ITR-1 activity. In contrast, IP(3) generated by PLC-beta appears to play little or no direct role in ITR-1 regulation. PLC-beta may function instead to control PIP(2) levels and/or G protein signaling events. Our findings provide new insights into intestinal cell Ca(2+) signaling mechanisms and establish C. elegans as a powerful model system for defining the gene networks and molecular mechanisms that underlie the generation and regulation of Ca(2+) oscillations and intercellular Ca(2+) waves in nonexcitable cells. |
| 巻・号 | 126(4) |
| ページ | 379-92 |
| 公開日 | 2005-10-1 |
| DOI | 10.1085/jgp.200509355 |
| PII | jgp.200509355 |
| PMID | 16186564 |
| PMC | PMC2266627 |
| MeSH | Animals Caenorhabditis elegans Calcium / metabolism* Calcium Channels / genetics Calcium Channels / metabolism* Calcium Signaling / physiology* Epithelial Cells / metabolism In Vitro Techniques Inositol 1,4,5-Trisphosphate / metabolism Inositol 1,4,5-Trisphosphate Receptors Intestinal Mucosa / metabolism* Intracellular Fluid / metabolism Isoenzymes / genetics Isoenzymes / metabolism* Muscle Contraction / physiology Mutation Myocytes, Smooth Muscle / metabolism Phospholipase C beta Phospholipase C gamma / genetics Phospholipase C gamma / metabolism* RNA Interference Receptors, Cytoplasmic and Nuclear / genetics Receptors, Cytoplasmic and Nuclear / metabolism* Time Factors Type C Phospholipases / genetics Type C Phospholipases / metabolism* |
| IF | 3.628 |
| 引用数 | 106 |
| WOS 分野 | PHYSIOLOGY |
| 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 | Policy sources |
| 各媒体での言及数の合計 | 2 |
| 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 | tm1340 |