Lysosome-sarcoplasmic reticulum junctions - A trigger zone for calcium signaling by nicotinic acid adenine dinucleotide phosphate and endothelin-1

Lysosome-sarcoplasmic reticulum junctions - A trigger zone for calcium signaling by nicotinic acid adenine dinucleotide phosphate and endothelin-1
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DOI:
10.1074/jbc.m406132200
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发表时间:
2004-12-24
影响因子:
4.8
通讯作者:
Evans, AM
Evans, AM
中科院分区:
生物学2区
文献类型:
--
作者:
Kinnear, NP;Boittin, FX;Evans, AM

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先前对肺动脉平滑肌细胞的研究表明,烟酸腺嘌呤二核苷酸磷酸(NAADP)通过动员thapsigarginin敏感储存唤起高度定位的细胞内Ca2+信号。这种局部Ca2+信号可能通过Ca2+诱导的Ca2+释放在肌浆网上募集ryanodine受体,从而引发全局Ca2+波和肌细胞收缩。在这里,我们表明NAADP通过动员巴菲霉素a1敏感的、溶酶体相关的Ca2+储存来唤起局部Ca2+信号。这些溶酶体通过与部分表达红嘌呤受体的肌浆网共定位来促进这一过程,形成一个高度特化的触发区,由血管收缩激素内皮素-1介导naadp依赖性Ca2+信号。这些发现进一步促进了我们对离散的空间组织的理解,细胞器Ca2+储存如何支持不同Ca2+动员信使产生差异Ca2+信号模式。
Previous studies on pulmonary arterial smooth muscle cells have shown that nicotinic acid adenine dinucleotide phosphate ( NAADP) evokes highly localized intracellular Ca2+ signals by mobilizing thapsigarginin-sensitive stores. Such localized Ca2+ signals may initiate global Ca2+ waves and contraction of the myocytes through the recruitment of ryanodine receptors on the sarcoplasmic reticulum via Ca2+-induced Ca2+ release. Here we show that NAADP evokes localized Ca2+ signals by mobilizing a bafilomycin A1-sensitive, lysosome-related Ca2+ store. These lysosomal stores facilitate this process by co-localizing with a portion of the sarcoplasmic reticulum expressing ryanodine receptors to comprise a highly specialized trigger zone for NAADP-dependent Ca2+ signaling by the vasoconstrictor hormone, endothelin-1. These findings further advance our understanding of how the spatial organization of discrete, organellar Ca2+ stores may underpin the generation of differential Ca2+ signaling patterns by different Ca2+-mobilizing messengers.