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Lysosomal Pathology and Osteopetrosis upon Loss of H+-Driven Lysosomal Cl- Accumulation.
- Source :
-
Science . 6/11/2010, Vol. 328 Issue 5984, p1401-1403. 3p. - Publication Year :
- 2010
-
Abstract
- During lysosomal acidification, proton-pump currents are thought to be shunted by a chloride ion (CD channel, tentatively identified as ClC-7. Surprisingly, recent data suggest that ClC-7 instead mediates G7proton (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 Clcn7unc/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 Clcn+/unc mice. Clcn7-/- and Clcn7un/unc mice accumulated less Cl- in lysosomes than did wild-type mice. Thus, lowered lysosomal chloride may underlie their common phenotypes. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00368075
- Volume :
- 328
- Issue :
- 5984
- Database :
- Academic Search Index
- Journal :
- Science
- Publication Type :
- Academic Journal
- Accession number :
- 51835244
- Full Text :
- https://doi.org/10.1126/science.1188072