Interaction of a farnesylated protein with renal type IIa Na/Pi co-transporter in response to parathyroid hormone and dietary phosphate

Ito, Mikiko; Iidawa, Sachi; Izuka, Michiyo; Haito, Sakiko; Segawa, Hiroko; Kuwahata, Masashi; Ohkido, Ichiro; Ohno, Hiroshi; Miyamoto, Ken‐ichi

doi:10.1042/bj20031223

Cited by 33 publications

(25 citation statements)

References 37 publications

(73 reference statements)

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“…Interestingly, an additional role for cytosolic rat Pex19p was proposed recently in internalization of a sodium-dependent phosphate co-transporter (40). Therefore, a portion of the cytosolic Pex19p in rat may function in another cellular process than peroxisome biogenesis, a phenomenon that deserves further attention in yeast research.…”

Section: Discussionmentioning

confidence: 99%

Hansenula polymorpha Pex19p Is Essential for the Formation of Functional Peroxisomal Membranes

Otzen

Perband

Wang

et al. 2004

Journal of Biological Chemistry

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We have cloned and characterized the Hansenula polymorpha PEX19 gene. In cells of a pex19 disruption strain (Hppex19), induced on methanol, peroxisome structures were not detectable; peroxisomal matrix proteins accumulated in the cytosol, whereas peroxisomal membrane proteins (PMPs) were mislocalized to the cytosol (Pex3p) and mitochondria (Pex14p) or strongly reduced to undetectable levels (Pex10p). The defect in peroxisome formation in Hppex19 cells was largely suppressed upon overproduction of HpPex3p or a fusion protein that consisted of the first 50 N-terminal amino acids of Pex3p and GFP. In these cells PMPs were again correctly sorted to peroxisomal structures, which also harbored peroxisomal matrix proteins. In Saccharomyces cerevisiae pex19 cells overproduction of ScPex3p led to the formation of numerous vesicles that contained PMPs but lacked the major matrix protein thiolase. Taken together, our data are consistent with a function of Pex19p in membrane protein assembly and function.Peroxisomes are single membrane-bound organelles that are present in virtually all eukaryotic cells. The biogenesis and maintenance of these organelles requires a fine-tuned orchestration of various processes, including among others protein sorting, membrane formation, and organelle fission. During the last 20 years the knowledge of the principles of peroxisome formation has rapidly expanded, and over 30 genes (designated PEX genes) have now been characterized that are involved in this process (for a recent review see Ref.

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Section: Discussionmentioning

confidence: 99%

Hansenula polymorpha Pex19p Is Essential for the Formation of Functional Peroxisomal Membranes

Otzen

Perband

Wang

et al. 2004

Journal of Biological Chemistry

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“…OK cells (clone 3B2), derived from opossum kidney, were kindly provided by Dr. J. Biber (Institute of Physiology, University of Zurich, Zurich, Switzerland) and were maintained in DMEM-F12 (Sigma) (17,35). The cell lines LLC-PK 1, derived from porcine kidney epithelia, Caco-2, derived from a human lung-metastasized intestinal carcinoma, and the MDCK cell line, derived from dog renal distal cells, were obtained from the RIKEN Bioresource Center (Tokyo, Japan).…”

Section: Methodsmentioning

confidence: 99%

“…For construction of the enhanced green fluorescent protein (EGFP)-NaPi-IIc fusion protein, wild-type (WT) mouse NaPi-IIc cotransporter (WT NaPi-IIc) cDNA was fused to the C terminus of EGFP by insertion of the full-length cDNA into the pEGFP-C1 vector (Stratagene, La Jolla, CA). For construction of human NaPi-IIa and mouse intestinal EGFP-NaPi-IIb fusion proteins, WT cDNA, including all coding sequences, was fused to the C terminus of EGFP (17). The N-terminal and C-terminal deletion mutants of NaPi-IIc were generated by PCR amplification using primers flanked by the appropriate restriction enzyme sites.…”

Section: Methodsmentioning

confidence: 99%

An apical expression signal of the renal type IIc Na⁺-dependent phosphate cotransporter in renal epithelial cells

Ito

Sakurai²,

Hayashi³

et al. 2010

American Journal of Physiology-Renal Physiology

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ϩ -dependent phosphate cotransporter (NaPi-IIc) is specifically targeted to, and expressed on, the apical membrane of renal proximal tubular cells and mediates phosphate transport. In the present study, we investigated the signals that determine apical expression of NaPi-IIc with a focus on the role of the N-and the C-terminal tails of mouse NaPi-IIc in renal epithelial cells [opossum kidney (OK) and Madin-Darby canine kidney cells]. Wild-type NaPi-IIc, the cotransporter NaPi-IIa, as well as several IIa-IIc chimeras and deletion mutants, were fused to enhanced green fluorescent protein (EGFP), and their cellular localization was analyzed in polarized renal epithelial cells by confocal microscopy and by cell-surface biotinylation. Fluorescent EGFP-fused NaPi-IIc transporter proteins are correctly expressed in the apical membrane of OK cells. The apical expression of N-terminal deletion mutants (deletion of N-terminal 25, 50, or 69 amino acids) was not affected by truncation. In contrast, C-terminal deletion mutants (deletion of C-terminal 45, 50, or 62 amino acids) did not have correct apical expression. A more detailed mutational analysis indicated that a domain (amino acids WLHSL) in the cytoplasmic C terminus is required for apical expression of NaPi-IIc in renal epithelial cells. We conclude that targeting of NaPi-IIc to the apical cell surface is regulated by a unique amino acid motif in the cytoplasmic C-terminal domain.Npt2c; SLC34A3; localization; OK cell; hereditary hypophosphatemic rickets with hypercalciuria INORGANIC PHOSPHATE (P i ) reabsorption in renal proximal tubules is required for P i homeostasis in the body. Na ϩ -dependent P i transporters (NaPi) in the brush-border membrane (BBM) of proximal tubule cells mediate the rate-limiting step in the overall P i -reabsorption process (26,28). Type IIa (NaPiIIa) and type IIc (NaPi-IIc) NaPi cotransporters are expressed in the apical membrane of proximal tubule cells and mediate P i transport (27, 38). The extent of P i reabsorption in the proximal tubules is determined largely by the abundance of the NaPi-IIa cotransporter (11,28,29).Several groups have shown that hereditary hypophosphatemic rickets with hypercalciuria (HHRH), a Mendelian disorder of renal P i reabsorption (39, 42), results from the lack of a functional NaPi-IIc protein, leading to severe renal wasting with hypophosphatemia (5,16,19,22,25). These data suggest that the NaPi-IIc cotransporter plays an important role in renal P i reabsorption and may be a key determinant of plasma P i concentrations in humans. However, it is not clear why a loss of function of the less abundant and energetically less favorable electroneutral NaPi-IIc transporter causes hypophosphatemia/rickets and osteomalacia in humans, whereas mutations in the more abundant electrogenic NaPi-IIa elicits a mild skeletal phenotype (3).The plasma membrane of epithelial cells is divided into two separate membrane compartments, the apical and the basolateral domains (36,37). This polarity is maintained by intracellular mach...

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“…The absence of this KR motif in the NaPi-llc protein could explain the different endocytic rates of the NaPi-lla and NaPi-llc cotransporters after PTH stimulation. It is of interest that the peroxisomal farnesylated protein PEX19 was reported to interact with NaPi-lla via the KR motif, yet the precise role of PEX19 in the trafficking of NaPi-lla has not been elucidated [54].…”

Section: Parathyroid Hormonementioning

confidence: 99%

Regulation of phosphate transport in proximal tubules

Biber

Hernando

Forster

et al. 2008

Pflugers Arch - Eur J Physiol

168

154

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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.

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Interaction of a farnesylated protein with renal type IIa Na/Pi co-transporter in response to parathyroid hormone and dietary phosphate

Cited by 33 publications

References 37 publications

Hansenula polymorpha Pex19p Is Essential for the Formation of Functional Peroxisomal Membranes

Hansenula polymorpha Pex19p Is Essential for the Formation of Functional Peroxisomal Membranes

An apical expression signal of the renal type IIc Na⁺-dependent phosphate cotransporter in renal epithelial cells

Regulation of phosphate transport in proximal tubules

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Interaction of a farnesylated protein with renal type IIa Na/Pi co-transporter in response to parathyroid hormone and dietary phosphate

Cited by 33 publications

References 37 publications

Hansenula polymorpha Pex19p Is Essential for the Formation of Functional Peroxisomal Membranes

Hansenula polymorpha Pex19p Is Essential for the Formation of Functional Peroxisomal Membranes

An apical expression signal of the renal type IIc Na+-dependent phosphate cotransporter in renal epithelial cells

Regulation of phosphate transport in proximal tubules

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An apical expression signal of the renal type IIc Na⁺-dependent phosphate cotransporter in renal epithelial cells