Protein/Protein Interactions (PDZ) in Proximal Tubules

Biber, Jürg; Gisler, Serge M.; Hernando, Nati; Murer, Heini

doi:10.1007/s00232-005-0738-7

Cited by 32 publications

(23 citation statements)

References 79 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Classical yeast twohybrid screens performed against the C-terminus of NaPi-lla revealed interactions of this cotransporter with several PDZ domain (PSD-95, discs-large, ZO-1) containing proteins that may contribute to the stabilization of NaPi-lla at the apical membrane (Fig. 2b) [15,[42][43][44]. Robust interactions of NaPi-lla with single PDZ domains of the sodiumhydrogen exchanger regulatory factor (NHERF), protein family [104], NHERF1 and 2, NHERF3 (PDZK1) and NHERF4 (PDZK2) have been demonstrated in in vitro studies.…”

Section: Na + /P I Cotransporters At Workmentioning

confidence: 99%

Regulation of phosphate transport in proximal tubules

Biber

Hernando

Forster

et al. 2008

Pflugers Arch - Eur J Physiol

Self Cite

168

154

View full text Add to dashboard Cite

Homeostasis of inorganic phosphate (P i ) is primarily an affair of the kidneys. Reabsorption of the bulk of filtered P i occurs along the renal proximal tubule and is initiated by apically localized Na + -dependent P i cotransporters. Tubular P i reabsorption and therefore renal excretion of P i is controlled by a number of hormones, including phosphatonins, and metabolic factors. In most cases, regulation of P i reabsorption is achieved by changing the apical abundance of Na + /Pi cotransporters. The regulatory mechanisms involve various signaling pathways and a number of proteins that interact with Na + /P i cotransporters.

show abstract

Section: Na + /P I Cotransporters At Workmentioning

confidence: 99%

Regulation of phosphate transport in proximal tubules

Biber

Hernando

Forster

et al. 2008

Pflugers Arch - Eur J Physiol

Self Cite

168

154

View full text Add to dashboard Cite

show abstract

“…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).…”

mentioning

confidence: 99%

mentioning

confidence: 99%

“…These domains consist of 80 -90 amino acids that very often (but not always) scaffold specific proteins into supramolecular complexes (17). Several PDZ domain-containing proteins interact with the COOH end of NaPiIIa (12), namely NHERF1 EBP50 (NHE3 Regulatory Factor 1) (34) and NHERF2 E3KARP (36), PDZK1 CAP70/NaPi-Cap1/NHERF3 (PDZ Protein of Kidney 1) (19) (now renamed NHERF3) (11), and PDZK2 NaPi-Cap2/NHERF4 (12) (now renamed NHERF4) (11), CAL PIST/GOPC/FIG (5,9), and Shank2E (26). In addition, several proteins interact with NaPiIIa independently of PDZ domains.…”

mentioning

confidence: 99%

See 1 more Smart Citation

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

Lanaspa¹,

Giral²,

Breusegem³

et al. 2007

American Journal of Physiology-Renal Physiology

View full text Add to dashboard Cite

.-The function of the NaPiIIa renal sodium-phosphate transporter is regulated through a complex network of interacting proteins. Several PDZ domain-containing proteins interact with its COOH terminus while the small membrane protein MAP17 interacts with its NH 2 end. To elucidate the function of MAP17, we identified its interacting proteins using both bacterial and mammalian two-hybrid systems. Several PDZ domain-containing proteins, including the four NHERF proteins, as well as NaPiIIa and NHE3, were found to bind to MAP17. The interactions of MAP17 with the NHERF proteins and with NaPiIIa were further analyzed in opossum kidney (OK) cells. Expression of MAP17 alone had no effect on the NaPiIIa apical membrane distribution, but coexpression of MAP17 and NHERF3 or NHERF4 induced internalization of NaPiIIa, MAP17, and the PDZ protein to the trans-Golgi network (TGN). This effect was not observed when MAP17 was cotransfected with NHERF1/2 proteins. Inhibition of protein kinase C (PKC) prevented expression of the three proteins in the TGN. Activation of PKC in OK cells transfected only with MAP17 induced complete degradation of MAP17 and NaPiIIa. When lysosomal degradation was prevented, both proteins accumulated in the TGN. When the dopamine D1-like receptor was activated with fenoldopam, both NaPiIIa and MAP17 also accumulated in the TGN. Finally, cotransfection of MAP17 and NHERF3 prevented the adaptive upregulation of phosphate transport activity in OK cells in response to low extracellular phosphate. Therefore, the interaction between MAP17, NHERF3/4, and NaPiIIa in the TGN could be an important intermediate or alternate path in the internalization of NaPiIIa. phosphate transport; PDZ; PDZK1; protein interaction; opossum kidney cells RENAL REABSORPTION OF INORGANIC phosphate (P i ) and its regulation involve molecular mechanisms more complicated than initially thought. 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). Several PDZ domain-containing proteins interact with the COOH end of NaPiIIa (12) DD96/SPAP is a small membrane protein that interacts with the NH 2 terminus of the phosphate transporter (28). MAP17 was first identified by differential display because its RNA was overexpressed in several carcinomas (18). In addition, it was also isolated during the expression cloning of a renal Na/D-mannose cotransport in Xenopus laevis oocytes, and it was considered to be an activator of a mannose transporter endogenous to the oocyte (6). Yeast two-hybrid experi...

show abstract

“…Recently (18), the Cterminus of PKD (both PKD1 and PKD2) was identified to contain a postsynaptic density-95 / discs large / zonula occludens-1 (PDZ)-binding motif, which are short peptide sequences that can bind to PDZ proteins containing 70 -90 amino acid PDZ domains. PDZ proteins are known to control the transport and function of membrane proteins (51,52). It has been suggested that PKD may regulate the translocation of proteins to the plasma membrane by its interaction with PDZ proteins (18).…”

Section: Discussionmentioning

confidence: 99%

Angiotensin II Directly Triggers Endothelial Exocytosis via Protein Kinase C-Dependent Protein Kinase D2 Activation

Low

Liang

et al. 2007

J Pharmacol Sci

View full text Add to dashboard Cite

Abstract. Angiotensin II (AII) has been reported to induce leukocyte adhesion to endothelium through up-regulation of P-selectin surface expression. However, the underlying molecular and cellular mechanisms remain unknown. P-selectin is stored in Weibel-Palade bodies (WPBs), large secretory granules, in endothelial cells. In this study, we examined the role of protein kinase D (PKD), a newly identified regulator of protein transport, in AII-induced WPB exocytosis and the resultant P-selectin surface expression. We demonstrated that PKD2 was rapidly activated by AII in endothelial cells through phosphorylation of the activation loop at Ser744/ 748. AII-induced PKD2 activation correlated with increased P-selectin surface expression. Furthermore, AII-regulated PKD2 activation is protein kinase C (PKC) α-dependent. Importantly, knock-down of either PKD2 or PKCα expression inhibited AII-mediated P-selectin surface expression and monocyte adhesion. Our findings provide the first evidence that stimulation of P-selectin surface expression via PKCα-dependent PKD2 activation could be an important mechanism in the early onset of AII-initiated endothelial adhesiveness.

show abstract

Protein/Protein Interactions (PDZ) in Proximal Tubules

Cited by 32 publications

References 79 publications

Regulation of phosphate transport in proximal tubules

Regulation of phosphate transport in proximal tubules

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

Angiotensin II Directly Triggers Endothelial Exocytosis via Protein Kinase C-Dependent Protein Kinase D2 Activation

Contact Info

Product

Resources

About