Grimm Christian, Chen Cheng-Chang, Wahl-Schott Christian, Biel Martin
Center for Integrated Protein Science Munich, Ludwig Maximilian University of MunichMunich, Germany; Department of Pharmacy - Center for Drug Research, Ludwig Maximilian University of MunichMunich, Germany.
Front Pharmacol. 2017 Feb 7;8:45. doi: 10.3389/fphar.2017.00045. eCollection 2017.
Two-pore channels (TPCs) have recently emerged as a novel class of non-selective cation channels in the endolysosomal system. There are two members in the human genome, TPC1 and TPC2. Studies with TPC knockout and knockdown models have revealed that these channels participate in the regulation of multiple endolysosomal trafficking pathways which when dysregulated can lead to or influence the development of a range of different diseases such as lysosomal storage, metabolic, or infectious diseases. TPCs have been demonstrated to be activated by different endogenous stimuli, PI(3,5)P and NAADP, and ATP has been found to block TPC activation via mTOR. Loss of TPCs can lead to obesity and hypercholesterolemia, and to a slow-down of intracellular virus and bacterial toxin trafficking, it can affect VEGF-induced neoangiogenesis, autophagy, human hair pigmentation or the acrosome reaction in sperm. Moreover, physiological roles of TPCs in cardiac myocytes and pancreatic β cells have been postulated.
双孔通道（TPCs）最近作为一种新型的非选择性阳离子通道出现在内溶酶体系统中。人类基因组中有两个成员，即TPC1和TPC2。对TPC基因敲除和敲低模型的研究表明，这些通道参与多种内溶酶体运输途径的调节，当这些途径失调时，可导致或影响一系列不同疾病的发生发展，如溶酶体贮积症、代谢性疾病或感染性疾病。已证明TPCs可被不同的内源性刺激物PI(3,5)P和NAADP激活，并且发现ATP可通过mTOR阻断TPC激活。TPCs缺失可导致肥胖和高胆固醇血症，并使细胞内病毒和细菌毒素运输减缓，它会影响血管内皮生长因子（VEGF）诱导的新生血管形成、自噬、人类毛发色素沉着或精子顶体反应。此外，还推测了TPCs在心肌细胞和胰腺β细胞中的生理作用。
