Title: | The yeast endosomal Na+K+/H+ exchanger Nhx1 regulates cellular pH to control vesicle trafficking |
Author(s): | Brett CL; Tukaye DN; Mukherjee S; Rao R; |
Address: | "Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA" |
ISSN/ISBN: | 1059-1524 (Print) 1059-1524 (Linking) |
Abstract: | "The relationship between endosomal pH and function is well documented in viral entry, endosomal maturation, receptor recycling, and vesicle targeting within the endocytic pathway. However, specific molecular mechanisms that either sense or regulate luminal pH to mediate these processes have not been identified. Herein we describe the use of novel, compartment-specific pH indicators to demonstrate that yeast Nhx1, an endosomal member of the ubiquitous NHE family of Na+/H+ exchangers, regulates luminal and cytoplasmic pH to control vesicle trafficking out of the endosome. Loss of Nhx1 confers growth sensitivity to low pH stress, and concomitant acidification and trafficking defects, which can be alleviated by weak bases. Conversely, weak acids cause wild-type yeast to present nhx1Delta trafficking phenotypes. Finally, we report that Nhx1 transports K+ in addition to Na+, suggesting that a single mechanism may responsible for both pH and K+-dependent endosomal processes. This presents the newly defined family of eukaryotic endosomal NHE as novel targets for pharmacological inhibition to alleviate pathological states associated with organellar alkalinization" |
Keywords: | "Biological Transport Cation Transport Proteins/*physiology Cytoplasm/metabolism Cytosol/metabolism Dose-Response Relationship, Drug Endosomes/*metabolism Green Fluorescent Proteins/chemistry/metabolism Hydrogen-Ion Concentration Microscopy, Confocal Model;" |
Notes: | "MedlineBrett, Christopher L Tukaye, Deepali N Mukherjee, Sanchita Rao, Rajini eng R01 DK054214/DK/NIDDK NIH HHS/ R01 DK54214/DK/NIDDK NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. 2005/01/07 Mol Biol Cell. 2005 Mar; 16(3):1396-405. doi: 10.1091/mbc.e04-11-0999. Epub 2005 Jan 5" |