Display Settings:

Format

Send to:

Choose Destination
See comment in PubMed Commons below
Mol Biol Cell. 2005 Mar;16(3):1396-405. Epub 2005 Jan 5.

The yeast endosomal Na+K+/H+ exchanger Nhx1 regulates cellular pH to control vesicle trafficking.

Author information

  • 1Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

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.

PMID:
15635088
[PubMed - indexed for MEDLINE]
PMCID:
PMC551501
Free PMC Article

Images from this publication.See all images (7)Free text

Figure 2.
Figure 1.
Figure 3.
Figure 4.
Figure 5.
Figure 6.
Figure 7.
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central Icon for Faculty of 1000
    Loading ...
    Write to the Help Desk