CLC genes are expressed in species from bacteria to human and encode Cl(-)-channels or Cl(-)/H(+)-exchangers. CLC proteins assemble to dimers, with each monomer containing an ion translocation pathway. Some mammalian isoforms need essential beta -subunits (barttin and Ostm1). Crystal structures of bacterial CLC Cl(-)/H(+)-exchangers, combined with transport analysis of mammalian and bacterial CLCs, yielded surprising insights into their structure and function. The large cytosolic carboxy-termini of eukaryotic CLCs contain CBS domains, which may modulate transport activity. Some of these have been crystallized. Mammals express nine CLC isoforms that differ in tissue distribution and subcellular localization. Some of these are plasma membrane Cl(-) channels, which play important roles in transepithelial transport and in dampening muscle excitability. Other CLC proteins localize mainly to the endosomal-lysosomal system where they may facilitate luminal acidification or regulate luminal chloride concentration. All vesicular CLCs may be Cl(-)/H(+)-exchangers, as shown for the endosomal ClC-4 and -5 proteins. Human diseases and knockout mouse models have yielded important insights into their physiology and pathology. Phenotypes and diseases include myotonia, renal salt wasting, kidney stones, deafness, blindness, male infertility, leukodystrophy, osteopetrosis, lysosomal storage disease and defective endocytosis, demonstrating the broad physiological role of CLC-mediated anion transport.

中文翻译：

---

CLC氯离子通道和转运蛋白：从基因到蛋白质结构，病理学和生理学。

CLC基因在从细菌到人类的物种中表达，并编码Cl（-）通道或Cl（-）/ H（+）交换子。CLC蛋白组装成二聚体，每个单体均包含离子易位途径。一些哺乳动物的同工型需要必需的β亚基（巴丁汀和Ostm1）。细菌CLC Cl（-）/ H（+）交换子的晶体结构，结合哺乳动物和细菌CLC的转运分析，产生了令人惊讶的洞察力，了解它们的结构和功能。真核CLC的大的胞质羧基末端含有CBS结构域，其可以调节转运活性。其中一些已经结晶。哺乳动物表达9种CLC亚型，在组织分布和亚细胞定位方面不同。其中一些是质膜Cl（-）通道，在跨上皮运输和抑制肌肉兴奋性中起重要作用。其他CLC蛋白主要定位于内体-溶酶体系统，在这些系统中它们可能促进腔内酸化或调节腔内氯化物浓度。所有囊泡CLC可能是Cl（-）/ H（+）交换子，如内体ClC-4和-5蛋白所示。人类疾病和基因敲除小鼠模型已对其生理学和病理学产生了重要见解。表型和疾病包括肌强直，肾盐消瘦，肾结石，耳聋，失明，男性不育，白细胞营养不良，骨质疏松症，溶酶体贮积病和胞吞缺陷，证明了CLC介导的阴离子转运的广泛生理作用。如对于内体ClC-4和-5蛋白所示。人类疾病和基因敲除小鼠模型已对其生理学和病理学产生了重要见解。表型和疾病包括肌强直，肾盐消瘦，肾结石，耳聋，失明，男性不育，白细胞营养不良，骨质疏松症，溶酶体贮积病和胞吞缺陷，证明了CLC介导的阴离子转运具有广泛的生理作用。如对于内体ClC-4和-5蛋白所示。人类疾病和基因敲除小鼠模型已对其生理学和病理学产生了重要见解。表型和疾病包括肌强直，肾盐消瘦，肾结石，耳聋，失明，男性不育，白细胞营养不良，骨质疏松症，溶酶体贮积病和胞吞缺陷，证明了CLC介导的阴离子转运具有广泛的生理作用。