article published Gaia Novarino author 3E57A680-F248-11E8-B48F-1D18A9856A870000-0002-7673-7178 Stefanie Weinert author Gesa Rickheit author Thomas Jentsch author Loss of the endosomal anion transport protein ClC-5 impairs renal endocytosis and underlies human Dent's disease. ClC-5 is thought to promote endocytosis by facilitating endosomal acidification through the neutralization of proton pump currents. However, ClC-5 is a 2 chloride (Cl-)/proton (H+) exchanger rather than a Cl- channel. We generated mice that carry the uncoupling E211A (unc) mutation that converts CLC-5 into a pure CL- conductor. Adenosine triphosphate (ATP)-dependent acidification of renal endosomes was reduced in mice in which ClC-5 was knocked out, but normal in Clcn5unc mice. However, their proximal tubular endocytosis was also impaired. Thus, endosomal chloride concentration, which is raised by CLC-5 in exchange for protons accumulated by the H+-ATPase, may play a role in endocytosis. American Association for the Advancement of Science2010 10.1126/science.1188070 32859841398 - 1401 yes G. Novarino, S. Weinert, G. Rickheit, T. Jentsch, Science 328 (2010) 1398–1401. Novarino G, Weinert S, Rickheit G, Jentsch T. Endosomal chloride-proton exchange rather than chloride conductance is crucial for renal endocytosis. <i>Science</i>. 2010;328(5984):1398-1401. doi:<a href="https://doi.org/10.1126/science.1188070">10.1126/science.1188070</a> Novarino, G., Weinert, S., Rickheit, G., &#38; Jentsch, T. (2010). Endosomal chloride-proton exchange rather than chloride conductance is crucial for renal endocytosis. <i>Science</i>. American Association for the Advancement of Science. <a href="https://doi.org/10.1126/science.1188070">https://doi.org/10.1126/science.1188070</a> Novarino G, Weinert S, Rickheit G, Jentsch T. 2010. Endosomal chloride-proton exchange rather than chloride conductance is crucial for renal endocytosis. Science. 328(5984), 1398–1401. Novarino, Gaia, et al. “Endosomal Chloride-Proton Exchange Rather than Chloride Conductance Is Crucial for Renal Endocytosis.” <i>Science</i>, vol. 328, no. 5984, American Association for the Advancement of Science, 2010, pp. 1398–401, doi:<a href="https://doi.org/10.1126/science.1188070">10.1126/science.1188070</a>. G. Novarino, S. Weinert, G. Rickheit, and T. Jentsch, “Endosomal chloride-proton exchange rather than chloride conductance is crucial for renal endocytosis,” <i>Science</i>, vol. 328, no. 5984. American Association for the Advancement of Science, pp. 1398–1401, 2010. Novarino, Gaia, Stefanie Weinert, Gesa Rickheit, and Thomas Jentsch. “Endosomal Chloride-Proton Exchange Rather than Chloride Conductance Is Crucial for Renal Endocytosis.” <i>Science</i>. American Association for the Advancement of Science, 2010. <a href="https://doi.org/10.1126/science.1188070">https://doi.org/10.1126/science.1188070</a>. 23102018-12-11T11:56:55Z2021-01-12T06:56:42Z