title: Organellar Na+/H+ exchangers: novel players in organelle pH regulation and their emerging functions.
abstract: Mammalian Na+/H+ exchangers (NHEs) play a fundamental role in cellular ion homeostasis. NHEs exhibit an appreciable variation in expression, regulation, and physiological function, dictated by their dynamics in subcellular localization and/or interaction with regulatory proteins. In recent years, a subgroup of NHEs consisting of four isoforms has been identified, and its members predominantly localize to the membranes of the Golgi apparatus and endosomes. These organellar NHEs constitute a family of transporters with an emerging function in the regulation of luminal pH and in intracellular membrane trafficking as expressed, for example, in cell polarity development. Moreover, specific roles of a variety of cofactors, regulating the intracellular dynamics of these transporters, are also becoming apparent, thereby providing further insight into their mechanism of action and overall functioning. Interestingly, organellar NHEs have been related to mental disorders, implying a potential role in the brain, thus expanding the physiological significance of these transporters.
authors.affiliation: Department of Biological Sciences, Graduate School of Science, Osaka University, 1-1 Machikaneyama, Toyonaka, Osaka, Japan.
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Ohgaki
authors.forename: Sven C D
authors.initials: SC
authors.lastname: van IJzendoorn
authors.forename: Masafumi
authors.initials: M
authors.lastname: Matsushita
authors.forename: Dick
authors.initials: D
authors.lastname: Hoekstra
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kanazawa
mesh_terms: D000136:Acid-Base Equilibrium / Q000235:genetics / Q000502:physiology; D000818:Animals; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007424:Intracellular Fluid / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D001523:Mental Disorders / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology; D051379:Mice; D015388:Organelles / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D020033:Protein Isoforms / Q000096:biosynthesis / Q000172:deficiency / Q000502:physiology; D021381:Protein Transport / Q000235:genetics / Q000502:physiology; D017923:Sodium-Hydrogen Exchangers / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014018:Tissue Distribution / Q000235:genetics / Q000502:physiology
chemical_list: C514888:NHE9 protein, mouse; D020033:Protein Isoforms; C445316:SLC9A6 protein, human; C429538:SLC9A7 protein, human; C486775:SLC9A8 protein, human; D017923:Sodium-Hydrogen Exchangers