Calcium signals regulated by NAADP and two-pore channels - their role in development, differentiation and cancer
Calcium signals regulated by NAADP and two-pore channels - their role in development, differentiation and cancer
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DOI：
10.1387/ijdb.150211jp
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发表时间：
2015-01-01
影响因子：
0.7
通讯作者：
Hachem, Alaa
中科院分区：
文献类型：
--
作者：
Parrington, John;Lear, Pamela;Hachem, Alaa
Ca 2+信号调节广泛的生理过程。细胞内Ca 2+库可以通过一系列信号转导机制响应细胞外刺激而动员，通常涉及可扩散的第二信使分子的募集。Ca 2+动员信使InsP（3）和cADPR分别通过InsP（3）和ryanodine受体从内质网释放Ca 2+，而第三信使NAADP从酸性内体和溶酶体释放Ca 2+。ER和酸性细胞器之间的双向通信与内溶酶体功能以及Ca 2+信号的产生具有功能相关性。双孔通道（TPC）目前是NAADP调节的Ca 2+通道的重要组成部分。Ca 2+信号已被证明在胚胎发育和细胞分化中发挥重要作用;然而，关于所涉及的确切信号传导机制仍有许多有待建立。NAADP和TPC在发育和分化中的作用的研究仍处于早期阶段，但最近的研究表明，它们在体内的关键发育阶段发挥重要作用，并且是体外神经元、骨骼肌细胞和破骨细胞分化的重要介质。NAADP信号和TPC也与自噬有关，自噬是分化中的一个重要过程。此外，最近已经确定了TPC 2与癌症之间的潜在联系。还需要进一步的研究来确定TPC的确切作用机制及其与NAADP信号传导的联系，并将其与细胞和生物体中分化和其他关键发育过程中的作用联系起来。
Ca2+ signals regulate a wide range of physiological processes. Intracellular Ca2+ stores can be mobilized in response to extracellular stimuli via a range of signal transduction mechanisms, often involving recruitment of diffusible second messenger molecules. The Ca2+ mobilizing messengers InsP(3) and cADPR release Ca2+ from the endoplasmic reticulum via InsP(3) and ryanodine receptors, respectively, while a third messenger, NAADP, releases Ca2+ from acidic endosomes and lysosomes. Bidirectional communication between the ER and acidic organelles has functional relevance for endolysosomal function as well as for the generation of Ca2+ signals. The two-pore channels (TPCs) are currently strong candidates for being key components of NAADP-regulated Ca2+ channels. Ca2+ signals have been shown to play important roles in embryonic development and cell differentiation; however, much remains to be established about the exact signalling mechanisms involved. Investigation of the role of NAADP and TPCs in development and differentiation is still at an early stage, but recent studies have suggested that they play important roles at key developmental stages in vivo and are important mediators of differentiation of neurons, skeletal muscle cells and osteoclasts in vitro. NAADP signals and TPCs have also been implicated in autophagy, an important process in differentiation. Moreover, potential links between TPC2 and cancer have been recently identified. Further studies will be required to identify the precise mechanisms of action of TPCs and their link with NAADP signalling, and to relate these to their roles in differentiation and other key developmental processes in the cell and organism.