SLC9/NHE gene family, a plasma membrane and organellar family of Na⁺/H⁺ exchangers

Abstract

This brief review of the human Na/H exchanger gene family introduces a new classification with three subgroups to the SLC9 gene family. Progress in the structure and function of this gene family is reviewed with structure based on homology to the bacterial Na/H exchanger NhaA. Human diseases which result from genetic abnormalities of the SLC9 family are discussed although the exact role of these transporters in causing any disease is not established, other than poorly functioning NHE3 in congenital Na diarrhea.

Fig. 1

Human sequences of SLC9 family were aligned using COBALT (Papadopoulos and Agarwala, 2007), a constraint-based alignment tool for multiple protein sequences. For NHE6, NHA1 and sperm-NHE which have spliced variants, the longest spliced variant (v1) is used for alignment. The radial tree was drawn by Drawtree.

Fig. 2

(a) Model of the transport domain of NHE1 showing the area of exchange as two opposing funnel structures facing the intracellular and extracellular surfaces with membrane spanning domains indicated by roman numerals with critical amino acids shown. (b) Comparison of NhaA and NHE1 transport domains, modeled from the crystal structure of NhaA. The homologus amino acids crucial to exchange of NhaA and NHE1 are show. (With permission from Donowitz et al., 2009, orginally from Landau et al., 2007)