An integrated mechanism of cardiomyocyte nuclear Ca(2+) signaling.
An integrated mechanism of cardiomyocyte nuclear Ca(2+) signaling.
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DOI：
10.1016/j.yjmcc.2014.06.015
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发表时间：
2014-10
影响因子：
5
通讯作者：
Lavandero S
中科院分区：
文献类型：
--
作者：
Ibarra C;Vicencio JM;Varas-Godoy M;Jaimovich E;Rothermel BA;Uhlén P;Hill JA;Lavandero S
在心肌细胞中，Ca 2+在控制收缩和调节基因表达的信号事件中起着核心作用。目前的证据表明，这两个关键功能之间的歧视是通过分离的Ca 2+内的亚细胞微区：转录是由Ca 2+释放核内微区，和兴奋收缩耦合调节胞质Ca 2+。因此，控制心肌细胞基因表达的多种激动剂，例如内皮素-1、血管紧张素-II或胰岛素样生长因子-1，共享触发核Ca 2+信号的特征。然而，信号转导途径耦合表面受体激活核Ca 2+释放，和表型反应，这样的信号，激动剂之间的不同。根据早期的假设，通过激活质膜受体来选择性控制核Ca 2+信号依赖于三磷酸肌醇受体在核膜上的战略定位。在那里，他们介导的钙释放从核周的钙2+商店后，结合三磷酸肌醇产生的细胞质，扩散到细胞核。最近，在核膜或核周肌膜内陷的这种受体的鉴定已经揭示了激动剂控制核Ca 2+释放的新机制。在这篇综述中，我们讨论了选择性控制核钙信号的机制，特别关注激动剂受体激活的新兴模型。
In cardiomyocytes, Ca2+ plays a central role in governing both contraction and signaling events that regulate gene expression. Current evidence indicates that discrimination between these two critical functions is achieved by segregating Ca2+ within subcellular microdomains: transcription is regulated by Ca2+ release within nuclear microdomains, and excitation–contraction coupling is regulated by cytosolic Ca2+. Accordingly, a variety of agonists that control cardiomyocyte gene expression, such as endothelin-1, angiotensin-II or insulin-like growth factor-1, share the feature of triggering nuclear Ca2+ signals. However, signaling pathways coupling surface receptor activation to nuclear Ca2+ release, and the phenotypic responses to such signals, differ between agonists. According to earlier hypotheses, the selective control of nuclear Ca2+ signals by activation of plasma membrane receptors relies on the strategic localization of inositol trisphosphate receptors at the nuclear envelope. There, they mediate Ca2+ release from perinuclear Ca2+ stores upon binding of inositol trisphosphate generated in the cytosol, which diffuses into the nucleus. More recently, identification of such receptors at nuclear membranes or perinuclear sarcolemmal invaginations has uncovered novel mechanisms whereby agonists control nuclear Ca2+ release. In this review, we discuss mechanisms for the selective control of nuclear Ca2+ signals with special focus on emerging models of agonist receptor activation.