Encoding of Ca2+ signals by differential expression of IP3 receptor subtypes
Encoding of Ca2+ signals by differential expression of IP3 receptor subtypes
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DOI：
10.1093/emboj/18.5.1303
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发表时间：
1999-03-01
期刊：
影响因子：
11.4
通讯作者：
Iino, M
中科院分区：
文献类型：
--
作者：
Miyakawa, T;Maeda, A;Iino, M
肌醇1，4，5-三磷酸（IP）在Ca 2+信号传导中起关键作用，其表现出控制重要细胞功能的多种时空模式。多种亚型的IP 3受体（IP 3R-1，-2和-3）表达的组织和发育特异性的方式，并形成异源四聚体通道，通过存储的Ca 2+释放，但IP 3R亚型的差异表达的生理意义是未知的。我们已经研究了表达单一或组合的IP 3 R亚型的基因工程B细胞中的Ca 2+信号传导机制，并表明Ca 2+信号传导模式取决于IP 3 R亚型，其对激动剂即IP 3、Ca 2+和ATP的反应显著不同，IP 3 R-2对IP 3最敏感，并且是持久的、在激活B细胞受体时发生的规则Ca 2+振荡中，IP 3R-1对ATP高度敏感，并介导不太规则的Ca 2+振荡。IP 3R-3对IP 3和Ca 2+最不敏感，并且倾向于产生双相Ca 2+瞬变。此外，我们第一次展示了共表达亚型之间的功能相互作用，我们的研究结果表明，IP 3R亚型的差异表达有助于编码IP 3介导的Ca 2+信号。
Inositol 1,4,5-trisphosphate (IP,) plays a key role in Ca2+ signalling, which exhibits a variety of spatiotemporal patterns that control important cell functions. Multiple subtypes of IP3 receptors (IP3R-1, -2 and -3) are expressed in a tissue- and development-specific manner and form heterotetrameric channels through which stored Ca2+ is released, but the physiological significance of the differential expression of IP3R subtypes is not known. We have studied the Ca2+-signalling mechanism in genetically engineered B cells that express either a single or a combination of IP3R subtypes, and show that Ca2+-signalling patterns depend on the IP3R subtypes, which differ significantly in their response to agonists, i.e. IP3, Ca2+ and ATP, IP3R-2 is the most sensitive to IP3 and is required for the long lasting, regular Ca2+ oscillations that occur upon activation of B-cell receptors, IP3R-1 is highly sensitive to ATP and mediates less regular Ca2+ oscillations. IP3R-3 is the least sensitive to IP3 and Ca2+, and tends to generate monophasic Ca2+ transients. Furthermore, we show for the first time functional interactions between coexpressed subtypes, Our results demonstrate that differential expression of IP3R subtypes helps to encode IP3-mediated Ca2+ signalling.