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Regulatory Binding Partners and Complexes of NHE3

Departments of Medicine and Physiology, GI Division, The Johns Hopkins University School of Medicine, Baltimore, Maryland

NHE3 is the brush-border (BB) Na⁺/H⁺ exchanger of small intestine, colon, and renal proximal tubule which is involved in large amounts of neutral Na⁺ absorption. NHE3 is a highly regulated transporter, being both stimulated and inhibited by signaling that mimics the postprandial state. It also undergoes downregulation in diarrheal diseases as well as changes in renal disorders. For this regulation, NHE3 exists in large, multiprotein complexes in which it associates with at least nine other proteins. This review deals with short-term regulation of NHE3 and the identity and function of its recognized interacting partners and the multiprotein complexes in which NHE3 functions.

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