Multiple modes of regulation of Na+/H+ exchangers.
Mammalian Na(+)/H(+) exchangers (NHE) mediate electroneutral countertransport of H(+) for Na(+) across the plasmalemmal and organellar membranes. They contribute to cellular and organellar pH and volume regulation and transepithelial Na(+) transport. The aim of this review is to illustrate the complex regulation of these transporters by focusing on the multiple mechanisms controlling the epithelial isoform, NHE3. A variety of agents and conditions (e.g., hormones, growth factors, cellular pH, and medium osmolarity) act in concert to achieve short-term and long-term regulation of this isoform. The underlying mechanism involves changes in the number of transporters on the cell surface and/or altered activity of the individual exchangers due to allosteric activation by intracellular protons, phosphorylation and interaction with accessory proteins and the cytoskeleton. A similar regulatory versatility probably applies to other NHE isoforms, and the lessons learned from studying members of the NHE family could serve as a useful reference when exploring the modes and levels of regulation of other transporters.
Hayashi
Hisayoshi
H
Cell Biology Programme, The Hospital for Sick Children, Toronto, Ontario, M5G 1X8, Canada.
Szászi
Katalin
K
Grinstein
Sergio
S
D000818:Animals; D001692:Biological Transport; D002462:Cell Membrane / Q000378:metabolism; D004594:Electrophysiology; D006728:Hormones / Q000502:physiology; D006863:Hydrogen-Ion Concentration; D007425:Intracellular Membranes / Q000378:metabolism; D010766:Phosphorylation; D011522:Protons; D012964:Sodium / Q000378:metabolism; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers / Q000235:genetics / Q000502:physiology*
D006728:Hormones; D011522:Protons; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers; D012964:Sodium