Kornak U, Kasper D, Bösl M R, Kaiser E, Schweizer M, Schulz A, Friedrich W, Delling G, Jentsch T J
Zentrum für Molekulare Neurobiologie Hamburg, ZMNH, Universität Hamburg, D-20246, Hamburg, Germany.
Cell. 2001 Jan 26;104(2):205-15. doi: 10.1016/s0092-8674(01)00206-9.
Chloride channels play important roles in the plasma membrane and in intracellular organelles. Mice deficient for the ubiquitously expressed ClC-7 Cl(-) channel show severe osteopetrosis and retinal degeneration. Although osteoclasts are present in normal numbers, they fail to resorb bone because they cannot acidify the extracellular resorption lacuna. ClC-7 resides in late endosomal and lysosomal compartments. In osteoclasts, it is highly expressed in the ruffled membrane, formed by the fusion of H(+)-ATPase-containing vesicles, that secretes protons into the lacuna. We also identified CLCN7 mutations in a patient with human infantile malignant osteopetrosis. We conclude that ClC-7 provides the chloride conductance required for an efficient proton pumping by the H(+)-ATPase of the osteoclast ruffled membrane.
氯离子通道在质膜和细胞内细胞器中发挥着重要作用。普遍表达的ClC-7氯离子通道缺陷的小鼠表现出严重的骨质石化和视网膜退化。尽管破骨细胞数量正常，但它们无法吸收骨组织，因为它们不能酸化细胞外吸收腔隙。ClC-7存在于晚期内体和溶酶体区室中。在破骨细胞中，它在由含H(+)-ATP酶的囊泡融合形成的皱褶膜中高度表达，该皱褶膜将质子分泌到腔隙中。我们还在一名人类婴儿恶性骨质石化患者中鉴定出CLCN7突变。我们得出结论，ClC-7为破骨细胞皱褶膜的H(+)-ATP酶高效泵浦质子提供了所需的氯电导。
