Referenced in: none

Automatically associated channels: ClC4 , ClC7

Title: Lysosomal pathology and osteopetrosis upon loss of H+-driven lysosomal Cl- accumulation.

Authors: Stefanie Weinert, Sabrina Jabs, Chayarop Supanchart, Michaela Schweizer, Niclas Gimber, Martin Richter, Jörg Rademann, Tobias Stauber, Uwe Kornak, Thomas J Jentsch

Journal, date & volume: Science, 2010 Jun 11 , 328, 1401-3

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/20430974

Abstract
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.