Extracellular Calcium Has Multiple Targets to Control Cell Proliferation
Extracellular Calcium Has Multiple Targets to Control Cell Proliferation
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DOI：
10.1007/978-3-319-26974-0_7
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发表时间：
2016-01-01
期刊：
影响因子：
--
通讯作者：
Capiod, Thierry
中科院分区：
文献类型：
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作者：
Capiod, Thierry
钙离子通道和G蛋白偶联的钙敏感受体（CaSR）和GPRC6a是细胞外钙信号传导的两种主要途径，它们调节肿瘤细胞的增殖、迁移和侵袭。许多细胞内信号传导途径对胞质钙升高敏感，相反，细胞内信号传导途径可以调节钙通道的表达和活性。钙通道无疑参与前者，而CaSR和GPRC6a最有可能干扰后者。至于神经递质，钙离子通过质膜通道和GPCR触发胞质游离钙浓度升高和细胞内信号传导和调节途径激活。钙敏感GPCR、CaSR和GPRC6a允许补充程度的控制，并且对于代谢型受体，它们不仅调节钙通道表达，而且还可以控制钙依赖性K+通道。所涉及的细胞内信号传导途径的多样性、它们对局部和整体细胞内钙增加以及对CaSR和GPRC6a刺激的敏感性、膜信号复合物的存在，所有这些赋予细胞将细胞外钙的作用转化为复杂的生理反应所需的可塑性，从而决定它们的命运。
Calcium channels and the two G-protein coupled receptors sensing extracellular calcium, calcium-sensing receptor (CaSR) and GPRC6a, are the two main means by which extracellular calcium can signal to cells and regulate many cellular processes including cell proliferation, migration and invasion of tumoral cells. Many intracellular signaling pathways are sensitive to cytosolic calcium rises and conversely intracellular signaling pathways can modulate calcium channel expression and activity. Calcium channels are undoubtedly involved in the former while the CaSR and GPRC6a are most likely to interfere with the latter. As for neurotransmitters, calcium ions use plasma membrane channels and GPCR to trigger cytosolic free calcium concentration rises and intracellular signaling and regulatory pathways activation. Calcium sensing GPCR, CaSR and GPRC6a, allow a supplemental degree of control and as for metabotropic receptors, they not only modulate calcium channel expression but they may also control calcium-dependent K+ channels. The multiplicity of intracellular signaling pathways involved, their sensitivity to local and global intracellular calcium increase and to CaSR and GPRC6a stimulation, the presence of membrane signalplex, all this confers the cells the plasticity they need to convert the effects of extracellular calcium into complex physiological responses and therefore determine their fate.