Boassa Daniela, Yool Andrea J
Program in Neuroscience, University of Arizona, Tucson 85721, USA.
Trends Pharmacol Sci. 2002 Dec;23(12):558-62. doi: 10.1016/s0165-6147(02)02112-0.
Aquaporin-1 (AQP1) is a member of the diverse major intrinsic protein family of water and solute channels. AQP1 is known as an osmotic water channel in kidney, brain, vascular system and other tissues, and recently has been demonstrated to function as a cation channel gated by cGMP. Electrophysiology and binding assays implicate direct cGMP binding in the AQP1 C-terminus and sequence similarities with cyclic-nucleotide-gated channels support the idea that the AQP1 C-terminus mediates ion channel activation. In this article, new data show that the AQP1 C-terminus also exhibits homology, at key residues, with the substrate-selectivity subdomain of cyclic nucleotide phosphodiesterases. Distinct pathways for fluxes of water and ions in the tetrameric AQP1 channel indicate an intriguing multifunctional capacity. The physiological role of AQP1 in transmembrane signaling remains to be elucidated for these channels expressed in native tissues.
水通道蛋白-1（AQP1）是水和溶质通道的主要内在蛋白家族中的一员。AQP1在肾脏、大脑、血管系统及其他组织中作为渗透水通道而为人所知，最近有研究表明它还可作为由环磷酸鸟苷（cGMP）门控的阳离子通道发挥作用。电生理学和结合分析表明cGMP直接结合于AQP1的C末端，且与环核苷酸门控通道的序列相似性支持了AQP1的C末端介导离子通道激活这一观点。在本文中，新数据表明AQP1的C末端在关键残基处也与环核苷酸磷酸二酯酶的底物选择性亚结构域具有同源性。四聚体AQP1通道中不同的水和离子通量途径表明其具有引人关注的多功能能力。对于在天然组织中表达的这些通道，AQP1在跨膜信号传导中的生理作用仍有待阐明。
