The role of SLC12A family of cation-chloride cotransporters and drug discovery methodologies.
The role of SLC12A family of cation-chloride cotransporters and drug discovery methodologies.
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DOI：
10.1016/j.jpha.2023.09.002
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发表时间：
2023-12
影响因子：
8.8
通讯作者：
Zhang, Jinwei
中科院分区：
文献类型：
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作者：
Zhang, Shiyao;Azlan, Nur Farah Meor;Josiah, Sunday Solomon;Zhou, Jing;Zhou, Xiaoxia;Jie, Lingjun;Zhang, Yanhui;Dai, Cuilian;Liang, Dong;Li, Peifeng;Li, Zhengqiu;Wang, Zhen;Wang, Yun;Ding, Ke;Wang, Yan;Zhang, Jinwei
The solute carrier family 12 (SLC12) of cation-chloride cotransporters (CCCs) comprises potassium chloride cotransporters (KCCs, e.g. KCC1, KCC2, KCC3, and KCC4)-mediated Cl− extrusion, and sodium potassium chloride cotransporters (N[K]CCs, NKCC1, NKCC2, and NCC)-mediated Cl− loading. The CCCs play vital roles in cell volume regulation and ion homeostasis. Gain-of-function or loss-of-function of these ion transporters can cause diseases in many tissues. In recent years, there have been considerable advances in our understanding of CCCs' control mechanisms in cell volume regulations, with many techniques developed in studying the functions and activities of CCCs. Classic approaches to directly measure CCC activity involve assays that measure the transport of potassium substitutes through the CCCs. These techniques include the ammonium pulse technique, radioactive or nonradioactive rubidium ion uptake-assay, and thallium ion-uptake assay. CCCs' activity can also be indirectly observed by measuring γ-aminobutyric acid (GABA) activity with patch-clamp electrophysiology and intracellular chloride concentration with sensitive microelectrodes, radiotracer 36Cl−, and fluorescent dyes. Other techniques include directly looking at kinase regulatory sites phosphorylation, flame photometry, 22Na+ uptake assay, structural biology, molecular modeling, and high-throughput drug screening. This review summarizes the role of CCCs in genetic disorders and cell volume regulation, current methods applied in studying CCCs biology, and compounds developed that directly or indirectly target the CCCs for disease treatments. CCCs are important for cellular chloride homeostasis. The genetics and distribution of CCCs and their dysregulation in disease conditions are described. Control mechanisms of CCCs in cell volume regulations are elaborated. Various methods for studying the functions and activities of CCCs are described. CCCs drug discovery by means of medicinal chemistry, cryo-EM, and HTP screening is summarized.
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影响因子：
3.8
作者：
Clemo, H F;Feher, J J;Baumgarten, C M
通讯作者：
Baumgarten, C M
影响因子：
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作者：
ASBURY, MJ;BOURKE, E;GATENBY, PBB
通讯作者：
GATENBY, PBB
影响因子：
5.3
作者：
Adragna NC;Ravilla NB;Lauf PK;Begum G;Khanna AR;Sun D;Kahle KT
通讯作者：
Kahle KT
影响因子：
64.8
作者：
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通讯作者：
Lifton, Richard P.
影响因子：
3.3
作者：
通讯作者：
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