Calcium-dependent clustering of inositol 1,4,5-trisphosphate receptors.
Calcium-dependent clustering of inositol 1,4,5-trisphosphate receptors.
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肌醇 1,4,5-三磷酸受体的钙依赖性聚集。
DOI：
10.1091/mbc.9.6.1465
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发表时间：
1998
影响因子：
3.3
通讯作者：
Wojcikiewicz,RJ
中科院分区：
文献类型：
--
作者：
Wilson,BS;Pfeiffer,JR;Smith,AJ;Oliver,JM;Oberdorf,JA;Wojcikiewicz,RJ
Rat basophilic leukemia (RBL-2H3) cells predominantly express the type II receptor for inositol 1,4,5-trisphosphate (InsP3), which operates as an InsP3-gated calcium channel. In these cells, cross-linking the high-affinity immunoglobulin E receptor (FcεR1) leads to activation of phospholipase C γ isoforms via tyrosine kinase- and phosphatidylinositol 3-kinase-dependent pathways, release of InsP3-sensitive intracellular Ca2+stores, and a sustained phase of Ca2+influx. These events are accompanied by a redistribution of type II InsP3receptors within the endoplasmic reticulum and nuclear envelope, from a diffuse pattern with a few small aggregates in resting cells to large isolated clusters after antigen stimulation. Redistribution of type II InsP3receptors is also seen after treatment of RBL-2H3 cells with ionomycin or thapsigargin. InsP3receptor clustering occurs within 5–10 min of stimulus and persists for up to 1 h in the presence of antigen. Receptor clustering is independent of endoplasmic reticulum vesiculation, which occurs only at ionomycin concentrations >1 μM, and maximal clustering responses are dependent on the presence of extracellular calcium. InsP3receptor aggregation may be a characteristic cellular response to Ca2+-mobilizing ligands, because similar results are seen after activation of phospholipase C-linked G-protein-coupled receptors; cholecystokinin causes type II receptor redistribution in rat pancreatoma AR4–2J cells, and carbachol causes type III receptor redistribution in muscarinic receptor-expressing hamster lung fibroblast E36M3Rcells. Stimulation of these three cell types leads to a reduction in InsP3receptor levels only in AR4–2J cells, indicating that receptor clustering does not correlate with receptor down-regulation. The calcium-dependent aggregation of InsP3receptors may contribute to the previously observed changes in affinity for InsP3in the presence of elevated Ca2+and/or may establish discrete regions within refilled stores with varying capacity to release Ca2+when a subsequent stimulus results in production of InsP3.
