钙(Ca2+)可以调节多种细胞命运,如扩散,凋亡,和自噬。更重要的是,细胞内Ca2+水平的变化可以调节信号通路,控制广泛的生理和病理细胞事件,包括那些对细胞兴奋性重要的,细胞周期,基因转录,收缩,癌症进展,等。不仅细胞内Ca2水平,而且细胞内区室中Ca2的分布也是一个高度调节的过程。对于这种Ca2+稳态,大量的Ca2+螯合,storage,和运输机制是必需的。还有专门的蛋白质负责Ca2+的缓冲和转运。T型Ca2通道(TTCC)是那些在许多可兴奋和不可兴奋细胞类型的信号转导中起关键作用的特化蛋白之一。TTCC是属于电压门控Ca2+通道家族的低电压激活通道。几十年来,多种激酶和磷酸酶已被证明可以调节TTCC的活性,从而在维持细胞生理学中起间接作用。在这次审查中,我们提供了有关TTCC亚型Cav3.1,Cav3.2和Cav3.3的激酶和磷酸酶调节的信息,这些亚型主要描述了与细胞兴奋性无关的作用.我们还描述了尚未探索的可能的潜在调制。例如,丝裂原活化蛋白激酶和柚子激酶都对不同的TTCC亚型显示出亲和力;然而,这种相互作用对TTCC电流/动力学的影响尚未研究。
Calcium (Ca2+) can regulate a wide variety of cellular fates, such as proliferation, apoptosis, and autophagy. More importantly, changes in the intracellular Ca2+ level can modulate signaling pathways that control a broad range of physiological as well as pathological cellular events, including those important to cellular excitability, cell cycle, gene-transcription, contraction, cancer progression, etc. Not only intracellular Ca2+ level but the distribution of Ca2+ in the intracellular compartments is also a highly regulated process. For this Ca2+ homeostasis, numerous Ca2+ chelating, storage, and transport mechanisms are required. There are also specialized proteins that are responsible for buffering and transport of Ca2+. T-type Ca2+ channels (TTCCs) are one of those specialized proteins which play a key role in the signal transduction of many excitable and non-excitable cell types. TTCCs are low-voltage activated channels that belong to the family of voltage-gated Ca2+ channels. Over decades, multiple kinases and phosphatases have been shown to modulate the activity of TTCCs, thus playing an indirect role in maintaining cellular physiology. In this review, we provide information on the kinase and phosphatase modulation of TTCC isoforms Cav3.1, Cav3.2, and Cav3.3, which are mostly described for roles unrelated to cellular excitability. We also describe possible potential modulations that are yet to be explored. For example, both mitogen-activated protein kinase and citron kinase show affinity for different TTCC isoforms; however, the effect of such interaction on TTCC current/kinetics has not been studied yet.