细胞生物学
骨质疏松症
溶酶体
表型
电导
氯离子通道
氯化物
溶酶体贮存病
化学
生物
生物物理学
分子生物学
生物化学
免疫学
组合数学
基因
有机化学
酶
数学
作者
Stefanie Weinert,Sabrina Jabs,Chayarop Supanchart,Michaela Schweizer,Niclas Gimber,Martin Richter,Jörg Rademann,Tobias Stauber,Uwe Kornak,Thomas J. Jentsch
出处
期刊:Science
[American Association for the Advancement of Science (AAAS)]
日期:2010-06-11
卷期号:328 (5984): 1401-1403
被引量:210
标识
DOI:10.1126/science.1188072
摘要
During lysosomal acidification, proton-pump currents are thought to be shunted by a chloride ion (Cl-) channel, tentatively identified as ClC-7. Surprisingly, recent data suggest that ClC-7 instead mediates Cl-/proton (H+) exchange. We generated mice carrying a point mutation converting ClC-7 into an uncoupled (unc) Cl- conductor. Despite maintaining lysosomal conductance and normal lysosomal pH, these Clcn7(unc/unc) mice showed lysosomal storage disease like mice lacking ClC-7. However, their osteopetrosis was milder, and they lacked a coat color phenotype. Thus, only some roles of ClC-7 Cl-/H+ exchange can be taken over by a Cl- conductance. This conductance was even deleterious in Clcn7(+/unc) mice. Clcn7(-/-) and Clcn7(unc/unc) mice accumulated less Cl- in lysosomes than did wild-type mice. Thus, lowered lysosomal chloride may underlie their common phenotypes.
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