GPHR is a novel anion channel critical for acidification and functions of the Golgi apparatus

Nat Cell Biol. 2008 Oct;10(10):1135-45. doi: 10.1038/ncb1773. Epub 2008 Sep 14.


The organelles within secretory and endocytotic pathways in mammalian cells have acidified lumens, and regulation of their acidic pH is critical for the trafficking, processing and glycosylation of cargo proteins and lipids, as well as the morphological integrity of the organelles. How organelle lumen acidification is regulated, and how luminal pH elevation disturbs these fundamental cellular processes, is largely unknown. Here, we describe a novel molecule involved in Golgi acidification. First, mutant cells defective in Golgi acidification were established that exhibited delayed protein transport, impaired glycosylation and Golgi disorganization. Using expression cloning, a novel Golgi-resident multi-transmembrane protein, named Golgi pH regulator (GPHR), was identified as being responsible for the mutant cells. After reconstitution in planar lipid bilayers, GPHR exhibited a voltage-dependent anion-channel activity that may function in counterion conductance. Thus, GPHR modulates Golgi functions through regulation of acidification.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • CHO Cells
  • Cricetinae
  • Cricetulus
  • Glycosylation
  • Golgi Apparatus / enzymology
  • Golgi Apparatus / metabolism*
  • Golgi Apparatus / ultrastructure
  • Humans
  • Ion Channels / chemistry
  • Ion Channels / metabolism*
  • Molecular Sequence Data
  • Mutation / genetics
  • Phenotype
  • Protein Biosynthesis
  • Protein Structure, Quaternary
  • Protein Transport
  • Vacuolar Proton-Translocating ATPases / metabolism


  • Ion Channels
  • Vacuolar Proton-Translocating ATPases