Molecular cloning and characterization of a novel (Na+,K+)/H+ exchanger localized to the trans-Golgi network.
The luminal pH of organelles along the secretory and endocytic pathways of mammalian cells is acidic and tightly regulated, with the [H+] varying up to 100-fold between compartments. Steady-state organellar pH is thought to reflect a balance between the rates of H+ pumping by the vacuolar-type H+-ATPase and H+ efflux through ill-defined pathways. Here, we describe the cloning of a novel gene (NHE7) in humans that is homologous to Na+/H+ exchangers, is ubiquitously expressed, and localizes predominantly to the trans-Golgi network. Significantly, NHE7 mediates the influx of Na+ or K+ in exchange for H+. The activity of NHE7 was also found to be relatively insensitive to inhibition by amiloride but could be antagonized by the analogue benzamil and the unrelated compound quinine. Thus, NHE7 displays unique functional and pharmacological properties and may play an important role in maintaining cation homeostasis of this important organelle.
Numata
M
M
Department of Physiology, McGill University, Montréal, Québec H3G 1Y6, Canada.
Orlowski
J
J
D000595:Amino Acid Sequence; D000818:Animals; D017920:Antiporters / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D016466:CHO Cells; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D003001:Cloning, Molecular; D006224:Cricetinae; D006801:Humans; D006863:Hydrogen-Ion Concentration; D026901:Membrane Transport Proteins; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011188:Potassium / Q000378:metabolism*; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D012964:Sodium / Q000378:metabolism*; D017923:Sodium-Hydrogen Exchangers; D014162:Transfection; D021601:trans-Golgi Network / Q000378:metabolism*
D017920:Antiporters; D002352:Carrier Proteins; D026901:Membrane Transport Proteins; D020033:Protein Isoforms; D011994:Recombinant Proteins; C429538:SLC9A7 protein, human; D017923:Sodium-Hydrogen Exchangers; D012964:Sodium; D011188:Potassium