Article

The role of NHERF‐1 in the regulation of renal proximal tubule sodium–hydrogen exchanger 3 and sodium‐dependent phosphate cotransporter 2a

Department of Medicine, Division of Nephrology, University of Maryland, School of Medicine, 22, South Greene Street, Baltimore, MD 21202, USA.
The Journal of Physiology (Impact Factor: 4.54). 09/2005; 567(Pt 1):27-32. DOI: 10.1113/jphysiol.2005.086777
Source: PubMed

ABSTRACT Adaptor proteins containing PDZ interactive domains have been recently identified to regulate the trafficking and activity of ion transporters and channels in epithelial tissue. In the renal proximal tubule, three PDZ adaptor proteins, namely NHERF-1, NHERF-2 and PDZK1, are expressed in the apical membrane, heterodimerize with one another, and, at least in vitro, are capable of binding to NHE3 and Npt2a, two major regulated renal proximal tubule apical membrane transporters. Studies using NHERF-1 null mice have begun to provide insights into the organization of these adaptor proteins and their specific interactions with NHE3 and Npt2a. Experiments using brush border membranes and cultured renal proximal tubule cells indicate a specific requirement for NHERF-1 for cAMP-mediated phosphorylation and inhibition of NHE3. NHERF-1 null mice demonstrate increased urinary excretion of phosphate associated with mistargeting of Npt2a to the apical membrane of renal proximal tubule cells. NHERF-1 null animals challenged with a low phosphate diet and proximal tubule cells from these animals cultured in a low phosphate media fail to adapt as well as wild-type mice. These studies indicate a unique requirement for NHERF-1 in cAMP regulation of NHE3 and in the trafficking of Npt2a.

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    • "Nonetheless, given the widespread use of the NHERF nomenclature in the literature we suggest naming each protein as a member of the NHERF gene family. Moreover, we proposed that they be named to recognize this association in the order of their cloning, rather than using their many current designations, which are shown in parentheses: NHERF1 (NHERF, EBP50) (Donowitz et al. 2005; Hernando et al. 2005; Thelin et al. 2005; Weinman et al. 2005), NHERF2 (E3KARP, TKY-1, SIP-1) (Donowitz et al. 2005; Hernando et al. 2005; Thelin et al. 2005; Weinman et al. 2005), NHERF3 (PDZK1, CLAMP, CAP70, DIPHOR-1, NaPi-CaP1) (Donowitz et al. 2005; Thelin et al. 2005; Weinman et al. 2005) NHERF4 (IKEPP, DIPHOR-2, NaPiCaP2) (Donowitz et al. 2005; Hernando et al. 2005; Thelin et al. 2005; Weinman et al. 2005). A common name is proposed to allow recognition of their relationships in their primary structures and their similar expression pattern in many cell types. "
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