The Sodium/Proton Exchanger NHE8 Regulates Late Endosomal Morphology and Function

Scott P. Lawrence, Nicholas A. Bright, J. Paul Luzio, Katherine Bowers, Jean E. Gruenberg
<span title="2010-10-15">2010</span> <i title="American Society for Cell Biology (ASCB)"> <a target="_blank" rel="noopener" href="" style="color: black;">Molecular Biology of the Cell</a> </i> &nbsp;
The pH and lumenal environment of intracellular organelles is considered essential for protein sorting and trafficking through the cell. We provide the first evidence that a mammalian NHE sodium (potassium)/proton exchanger, NHE8, plays a key role in the control of protein trafficking and endosome morphology. At steady state, the majority of epitope-tagged NHE8 was found in the trans-Golgi network of HeLa M-cells, but a proportion was also localized to multivesicular bodies (MVBs). Depletion of
more &raquo; ... NHE8 in HeLa M-cells with siRNA resulted in the perturbation of MVB protein sorting, as shown by an increase in epidermal growth factor degradation. Additionally, NHE8-depleted cells displayed striking perinuclear clustering of endosomes and lysosomes, and there was a ninefold increase in the cellular volume taken up by LAMP1/ LBPA-positive, dense MVBs. Our data points to a role for the ion exchange activity of NHE8 being required to maintain endosome morphology, as overexpression of a nonfunctional point mutant protein (NHE8 E225Q) resulted in phenotypes similar to those seen after siRNA depletion of endogenous NHE8. Interestingly, we found that depletion of NHE8, despite its function as a sodium (potassium)/proton antiporter, did not affect the overall pH inside dense MVBs.
<span class="external-identifiers"> <a target="_blank" rel="external noopener noreferrer" href="">doi:10.1091/mbc.e09-12-1053</a> <a target="_blank" rel="external noopener" href="">pmid:20719963</a> <a target="_blank" rel="external noopener" href="">pmcid:PMC2954119</a> <a target="_blank" rel="external noopener" href="">fatcat:x77qful76bedjcnle32k7uwope</a> </span>
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