title: GPHR is a novel anion channel critical for acidification and functions of the Golgi apparatus.
abstract: 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.
authors.affiliation: Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871, Japan. ymaeda@biken.osaka-u.ac.jp
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Maeda
authors.forename: Toru
authors.initials: T
authors.lastname: Ide
authors.forename: Masato
authors.initials: M
authors.lastname: Koike
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Uchiyama
authors.forename: Taroh
authors.initials: T
authors.lastname: Kinoshita
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D006031:Glycosylation; D006056:Golgi Apparatus / Q000201:enzymology / Q000378:metabolism* / Q000648:ultrastructure; D006801:Humans; D007473:Ion Channels / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D014176:Protein Biosynthesis; D020836:Protein Structure, Quaternary; D021381:Protein Transport; D025262:Vacuolar Proton-Translocating ATPases / Q000378:metabolism
chemical_list: D007473:Ion Channels; D025262:Vacuolar Proton-Translocating ATPases