She Ji, Guo Jiangtao, Jiang Youxing
MOE Key Laboratory for Cellular Dynamics, School of Life Sciences, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui, China.
Department of Biophysics, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
Handb Exp Pharmacol. 2023;278:155-180. doi: 10.1007/164_2022_599.
Two-pore channels (TPCs) belong to the family of voltage-gated tetrameric cation channels and are ubiquitously expressed in organelles of animals and plants. These channels are believed to be evolutionary intermediates between homotetrameric voltage-gated potassium/sodium channels and the four-domain, single subunit, voltage-gated sodium/calcium channels. Each TPC subunit contains 12 transmembrane segments that can be divided into two homologous copies of an S1-S6 Shaker-like 6-TM domain. A functional TPC channel assembles as a dimer - the equivalent of a voltage-gated tetrameric cation channel. The plant TPC channel is localized in the vacuolar membrane and is also called the SV channel for generating the slow vacuolar (SV) current observed long before its molecular identification. Three subfamilies of mammalian TPC channels have been defined - TPC1, 2, and 3 - with the first two being ubiquitously expressed in animals and TPC3 being expressed in some animals but not in humans. Mammalian TPC1 and TPC2 are localized to the endolysosomal membrane and their functions are associated with various physiological processes. TPC3 is localized in the plasma membrane and its physiological function is not well defined.
双孔通道（TPCs）属于电压门控四聚体阳离子通道家族，在动植物细胞器中广泛表达。这些通道被认为是同型四聚体电压门控钾/钠通道与四结构域、单亚基电压门控钠/钙通道之间的进化中间体。每个TPC亚基包含12个跨膜片段，可分为两个S1-S6类Shaker 6-TM结构域的同源拷贝。功能性TPC通道组装为二聚体——相当于电压门控四聚体阳离子通道。植物TPC通道定位于液泡膜，在其分子鉴定之前很久就被观察到能产生慢液泡（SV）电流，因此也被称为SV通道。哺乳动物TPC通道已被定义为三个亚家族——TPC1、2和3——前两个在动物中广泛表达，TPC3在一些动物中表达，但在人类中不表达。哺乳动物TPC1和TPC2定位于内溶酶体膜，其功能与各种生理过程相关。TPC3定位于质膜，其生理功能尚不清楚。
