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ClC-7 drives intraphagosomal chloride accumulation to support hydrolase activity and phagosome resolution

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Item Type:Article
Title:ClC-7 drives intraphagosomal chloride accumulation to support hydrolase activity and phagosome resolution
Creators Name:Wu, J.Z. and Zeziulia, M. and Kwon, W. and Jentsch, T.J. and Grinstein, S. and Freeman, S.A.
Abstract:Degradative organelles contain enzymes that function optimally at the acidic pH generated by the V-ATPase. The resulting transmembrane H+ gradient also energizes the secondary transport of several solutes, including Cl-. We report that Cl- influx, driven by the 2Cl-/H+ exchanger ClC-7, is necessary for the resolution of phagolysosomes formed by macrophages. Cl- transported via ClC-7 had been proposed to provide the counterions required for electrogenic H+ pumping. However, we found that deletion of ClC-7 had a negligible effect on phagosomal acidification. Instead, luminal Cl- was found to be required for activation of a wide range of phagosomal hydrolases including proteases, nucleases, and glycosidases. These findings argue that the primary role of ClC-7 is the accumulation of (phago)lysosomal Cl- and that the V-ATPases not only optimize the activity of degradative hydrolases by lowering the pH but, importantly, also play an indirect role in their activation by providing the driving force for accumulation of luminal Cl- that stimulates hydrolase activity allosterically.
Keywords:Chloride Channels, Chlorides, Hydrogen-Ion Concentration, Hydrolases, Lysosomes, Phagosomes
Source:Journal of Cell Biology
Publisher:Rockefeller University Press
Page Range:e202208155
Date:5 June 2023
Additional Information:© 2023 Wu et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/).
Official Publication:https://doi.org/10.1083/jcb.202208155
PubMed:View item in PubMed

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