Cystic fibrosis transmembrane conductance regulator contributes to reacidification of alkalinized lysosomes in RPE cells.

American Journal of Physiology. Cell Physiology
Ji LiuClaire H Mitchell

Abstract

The role of the cystic fibrosis transmembrane conductance regulator (CFTR) in lysosomal acidification has been difficult to determine. We demonstrate here that CFTR contributes more to the reacidification of lysosomes from an elevated pH than to baseline pH maintenance. Lysosomal alkalinization is increasingly recognized as a factor in diseases of accumulation, and we previously showed that cAMP reacidified alkalinized lysosomes in retinal pigmented epithelial (RPE) cells. As the influx of anions to electrically balance proton accumulation may enhance lysosomal acidification, the contribution of the cAMP-activated anion channel CFTR to lysosomal reacidification was probed. The antagonist CFTR(inh)-172 had little effect on baseline levels of lysosomal pH in cultured human RPE cells but substantially reduced the reacidification of compromised lysosomes by cAMP. Likewise, CFTR activators had a bigger impact on cells whose lysosomes had been alkalinized. Knockdown of CFTR with small interfering RNA had a larger effect on alkalinized lysosomes than on baseline levels. Inhibition of CFTR in isolated lysosomes altered pH. While CFTR and Lamp1 were colocalized, treatment with cAMP did not increase targeting of CFTR to the lysosome. The...Continue Reading

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Citations

May 21, 2013·Acta Pharmacologica Sinica·Joseph J Babcock, Min Li
Aug 25, 2015·Molecular Therapy : the Journal of the American Society of Gene Therapy·Ruchira SinghDavid M Gamm
Feb 3, 2015·The Journal of Clinical Investigation·Jinghua LiuLane L Clarke
Aug 22, 2013·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Sonia GuhaClaire H Mitchell
Apr 2, 2021·Frontiers in Cellular Neuroscience·Keith E Campagno, Claire H Mitchell
Aug 19, 2020·Journal of Agricultural and Food Chemistry·Yuting LiWei Chen

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