Molecular mechanisms governing aquaporin relocalisation.
Molecular mechanisms governing aquaporin relocalisation.
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DOI：
10.1016/j.bbamem.2021.183853
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发表时间：
2022-04-01
期刊：
影响因子：
--
通讯作者：
Kitchen P
中科院分区：
文献类型：
--
作者：
Markou A;Unger L;Abir-Awan M;Saadallah A;Halsey A;Balklava Z;Conner M;Törnroth-Horsefield S;Greenhill SD;Conner A;Bill RM;Salman MM;Kitchen P
水通道蛋白（AQPs）形成了一个完整的膜蛋白家族，通过渗透促进水在生物膜上的运动，并促进小极性溶质的扩散。aqp已被认为是与水或溶质运输中断相关的各种疾病的药物靶点，包括中风或创伤后的脑水肿、癫痫、癌细胞迁移和肿瘤血管生成、代谢紊乱和炎症。尽管如此，由于缺乏可重复的高通量测定方法以及AQP蛋白的可药物性方面的困难，AQP的药物发现进展甚微。然而，最近的研究表明，靶向AQP蛋白到质膜的运输是一种可行的替代药物靶点，可以直接抑制导水孔。在这里，我们回顾了有关哺乳动物AQPs贩运的文献，以期突出与水和溶质稳态破坏相关的各种疾病的潜在新药靶点。水通道蛋白（AQPs）在生物膜上形成水和溶质渗透孔。aqp是水/溶质稳态紊乱的有吸引力的药物靶点。针对孔隙阻断AQP抑制剂的药物发现工作进展甚微。aqp在胞内囊泡和质膜之间动态地重新定位。这种重定位是抑制AQP功能的新靶点。
The aquaporins (AQPs) form a family of integral membrane proteins that facilitate the movement of water across biological membrane by osmosis, as well as facilitating the diffusion of small polar solutes. AQPs have been recognised as drug targets for a variety of disorders associated with disrupted water or solute transport, including brain oedema following stroke or trauma, epilepsy, cancer cell migration and tumour angiogenesis, metabolic disorders, and inflammation. Despite this, drug discovery for AQPs has made little progress due to a lack of reproducible high-throughput assays and difficulties with the druggability of AQP proteins. However, recent studies have suggested that targetting the trafficking of AQP proteins to the plasma membrane is a viable alternative drug target to direct inhibition of the water-conducting pore. Here we review the literature on the trafficking of mammalian AQPs with a view to highlighting potential new drug targets for a variety of conditions associated with disrupted water and solute homeostasis. Aquaporins (AQPs) form water and solute permeable pores in biological membranes. AQPs represent attractive drug targets for disorders of water/solute homeostasis. Drug discovery efforts towards pore-blocking AQP inhibitors have made little progress. AQPs are dynamically relocalised between intracellular vesicles and plasma membrane. This relocalisation represents a new target for inhibition of AQP function.
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DOI：
10.1074/jbc.m111.329219
发表时间：
2012-03-30
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Conner MT;Conner AC;Bland CE;Taylor LH;Brown JE;Parri HR;Bill RM
通讯作者：
Bill RM
前列腺癌中水通道蛋白 3 的亚细胞定位受 RalA 调节
影响因子：
4.2
作者：
Chen, Qiwei;Zhu, Liang;Wang, Jianbo
通讯作者：
Wang, Jianbo
影响因子：
11.4
作者：
Bestetti, Stefano;Galli, Mauro;Medrano-Fernandez, Iria
通讯作者：
Medrano-Fernandez, Iria
DOI：
10.1073/pnas.0712338105
发表时间：
2008-02-26
影响因子：
11.1
作者：
Fenton, Robert A.;Moeller, Hanne B.;Knepper, Mark A.
通讯作者：
Knepper, Mark A.
影响因子：
5.6
作者：
Bragiel, Aneta M.;Wang, Di;Ishikawa, Yasuko
通讯作者：
Ishikawa, Yasuko