The Role of the NHERF Family of PDZ Scaffolding Proteins in the Regulation of Salt and Water Transport Lessons Learned from Knockout Mice

The four members of the NHERF (Na+/H+ exchanger regulatory factor) family of PDZ adapter proteins bind to a variety of membrane transporters and receptors and modulate membrane expression, mobility, interaction with other proteins, and the formation of signaling complexes. All four family members are expressed in the intestine. The CFTR (cystic fibrosis transmembrane regulator) anion channel and the Na+/H+ exchanger NHE3 (Na/H exchanger-isoform 3) are two prominent binding partners to this PDZ-adapter family, which are also known key players in the regulation of intestinal electrolyte and fluid transport. Experiments in heterologous expression systems have provided a number of mechanistic models how NHERF protein interactions can affect the function of their targets at the molecular level. Recently, NHERF 1, 2, and 3 knockout mice have become available, and this review summarizes the reports on electrolyte and fluid transport regulation in the native intestine of these mice.