Structure, Function and Growth Factor Activation of the Na+/H+ Antiporter(NHE1)

The Na+/H+ exchanger NHE1 is an ubiquituously expressed transmembrane protein which is involved in intracellular pH and cell volume regulation. It is blocked by the compound amiloride and activated by all known mitogens and has therefore been hypothesized to be involved in cell proliferation control. In addition, several other isoforms of the Na+/H+ anti-porter (NHE2, NHE3, etc.) possessing a distinct pharmacological profile have been documented to perform specialized sodium transport across small intestine and kidney proximal tubule epithelia. In this review article we first describe the results obtained by a genetic approach which has led us to the molecular identification of the Na+/H+ antiporter NHE1 cDNA, and the characterization of the corresponding protein. The second part presents progress concerning the molecular mechanism of NHE1 activation by growth factors, the molecular identification of its amiloride-binding site and the sequence analysis of recently cloned cDNAs coding for various Na+/H+ antiporter isoforms pointing out the conserved domains which are presumed to be involved in ion translocation and internal pH sensing.