NaPi‐IIa and interacting partners

Abstract

Regulation of renal proximal tubular reabsorption of phosphate (P i ) is one of the critical steps in P i homeostasis. Experimental evidence suggests that this regulation is achieved mainly by controlling the apical expression of the Na + -dependent P i cotransporter type IIa (NaPi-IIa) in proximal tubules. Only recently have we started to obtain information regarding the molecular mechanisms that control the apical expression of NaPi-IIa. The first critical observation was the finding that truncation of only its last three amino acid residues has a strong effect on apical expression. A second major finding was the observation that the last intracellular loop of NaPi-IIa contains sequence information that confers parathyroid hormone (PTH) sensitivity. The use of the above domains of the cotransporter in yeast two-hybrid (Y2H) screening allowed the identification of proteins interacting with NaPi-IIa. Biochemical and morphological, as well as functional, analyses have allowed us to obtain insights into the physiological roles of such interactions, although our present knowledge is still far from complete.

Tissue-specific Regulation of Sodium/Proton Exchanger Isoform 3 Activity in Na+/H+ Exchanger Regulatory Factor 1 (NHERF1) Null Mice

“…The Na ϩ /H ϩ exchanger regulatory factor (NHERF) 2 family of multi-PDZ domain proteins consists of four homologous and evolutionarily related proteins (1)(2)(3)(4). In renal proximal tubule and small intestinal epithelial cells, all four NHERF proteins are present in the apical domain either in the brush border (BB) or just below it (Refs.…”

NHERF3 (PDZK1) Contributes to Basal and Calcium Inhibition of NHE3 Activity in Caco-2BBe Cells

“…NHERF1 and NHERF2 have been previously shown to contribute to acute NHE3 stimulation and inhibition (3)(4)(5)(6)(7)(8)(9)(10). Recently, two additional PDZ domain containing proteins, termed NHERF3/ PDZK1 and NHERF4/PDZK2/IKEPP, have been demonstrated to possess sequence homology with NHERF1 and NHERF2 (11)(12)(13)(14). However, unlike NHERF1 and NHERF2, which are comprised of two tandem PDZ domains flanked by a C-terminal ezrin/radixin/moesin binding domain, NHERF3 and NHERF4 consist of four PDZ domains but no other proteinprotein interacting domains (12).…”

Interaction of MAP17 with NHERF3/4 induces translocation of the renal Na/Pi IIa transporter to thetrans-Golgi

“…After expression cloning of NaPiIIa (24), the transporter responsible for most renal P i reabsorption, a complex network of interacting proteins that modulate the activity of this transporter has been described (for reviews, see Refs. 4,5,15,35).…”

“…After expression cloning of NaPiIIa (24), the transporter responsible for most renal P i reabsorption, a complex network of interacting proteins that modulate the activity of this transporter has been described (for reviews, see Refs. 4,5,15,35).Most of the proteins that interact with this transporter contain one or more PDZ domains (acronym of the postsynaptic density protein PSD-95, the Drosophila junctional protein Disc-large, and the tight junction protein ZO1). These domains consist of 80 -90 amino acids that very often (but not always) scaffold specific proteins into supramolecular complexes (17).…”