NHERF: targeting and trafficking membrane proteins

Am J Physiol Renal Physiol. 2001 Mar;280(3):F389-95. doi: 10.1152/ajprenal.2001.280.3.F389.


Vectorial ion transport initiated by Na+/H+ exchanger isoform 3 (NHE3) mediates the reabsorption of NaCl and NaHCO(3) in renal proximal tubule cells. NHE3 activity is modulated by numerous physiological stimuli. Biochemical and cellular experiments identified Na+/H+ exchanger regulatory factor (NHERF) as a protein cofactor essential for cAMP-mediated inhibition of NHE3 activity. Identification of numerous NHERF targets, including several transmembrane receptors and ion transporters, has broadened the role of this PSD-95/Dlg-1, Drososphila disk large/ZO-1 domain-containing adapter protein in membrane physiology. NHERF also associates with members of the ezrin/radixin/moesin family of actin-binding proteins and thus links NHE3 to the actin cytoskeleton. Formation of this multiprotein complex facilitates NHE3 phosphorylation and hormonal control of Na+/H+ exchange. NHERF also plays a critical role in targeting transport proteins to apical membranes. Moreover, the NHERF signaling complex functions as a regulatory unit to control endocytosis and internal trafficking of membrane proteins. This article reviews the new evidence that implicates NHERF in wider aspects of epithelial membrane biology.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Animals
  • Cytoskeletal Proteins
  • Cytoskeleton / physiology
  • Endocytosis / physiology
  • Membrane Proteins / physiology
  • Phosphoproteins / metabolism
  • Phosphoproteins / physiology*
  • Phosphorylation
  • Sodium-Hydrogen Exchanger 3
  • Sodium-Hydrogen Exchangers / physiology


  • Cytoskeletal Proteins
  • Membrane Proteins
  • Phosphoproteins
  • Sodium-Hydrogen Exchanger 3
  • Sodium-Hydrogen Exchangers
  • ezrin
  • sodium-hydrogen exchanger regulatory factor