ClC-7 drives intraphagosomal chloride accumulation to support hydrolase activity and phagosome resolution
| العنوان: | ClC-7 drives intraphagosomal chloride accumulation to support hydrolase activity and phagosome resolution |
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| المؤلفون: | Jing Ze Wu, Mariia Zeziulia, Whijin Kwon, Thomas J. Jentsch, Sergio Grinstein, Spencer A. Freeman |
| المصدر: | Journal of Cell Biology. 222 |
| بيانات النشر: | Rockefeller University Press, 2023. |
| سنة النشر: | 2023 |
| مصطلحات موضوعية: | Cell Biology |
| الوصف: | 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. |
| تدمد: | 1540-8140 0021-9525 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::527166d77285493841d08b23f8f3f2ac https://doi.org/10.1083/jcb.202208155 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi...........527166d77285493841d08b23f8f3f2ac |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15408140 00219525 |
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