Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Clin Exp Nephrol
2019 Mar 01;233:313-324. doi: 10.1007/s10157-018-1653-4.
Show Gene links
Show Anatomy links
Analysis of opossum kidney NaPi-IIc sodium-dependent phosphate transporter to understand Pi handling in human kidney.
Fujii T
,
Shiozaki Y
,
Segawa H
,
Nishiguchi S
,
Hanazaki A
,
Noguchi M
,
Kirino R
,
Sasaki S
,
Tanifuji K
,
Koike M
,
Yokoyama M
,
Arima Y
,
Kaneko I
,
Tatsumi S
,
Ito M
,
Miyamoto KI
.
???displayArticle.abstract???
BACKGROUND: The role of Na+-dependent inorganic phosphate (Pi) transporters in the human kidney is not fully clarified. Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is caused by loss-of-function mutations in the IIc Na+-dependent Pi transporter (NPT2c/Npt2c/NaPi-IIc) gene. Another Na+-dependent type II transporter, (NPT2A/Npt2a/NaPi-IIa), is also important for renal Pi reabsorption in humans. In mice, Npt2c deletion does not lead to hypophosphatemia and rickets because Npt2a compensates for the impaired Pi reabsorption. To clarify the differences between mouse and human, we investigated the relation between NaPi-IIa and NaPi-IIc functions in opossum kidney (OK) cells.
METHODS: We cloned NaPi-IIc from OK cells and created opossum NaPi-IIc (oNaPi-IIc) antibodies. We used oNaPi-IIc small interference (si)RNA and investigated the role of NaPi-IIc in Pi transport in OK cells.
RESULTS: We cloned opossum kidney NaPi-IIc cDNAs encoding 622 amino acid proteins (variant1) and examined their pH- and sodium-dependency. The antibodies reacted specifically with 75-kDa and 150-kDa protein bands, and the siRNA of NaPi-IIc markedly suppressed endogenous oNaPi-IIc in OK cells. Treatment with siRNA significantly suppressed the expression of NaPi-4 (NaPi-IIa) protein and mRNA. oNaPi-IIc siRNA also suppressed Na+/H+ exchanger regulatory factor 1 expression in OK cells.
CONCLUSION: These findings suggest that NaPi-IIc is important for the expression of NaPi-IIa (NaPi-4) protein in OK cells. Suppression of Npt2c may downregulate Npt2a function in HHRH patients.
Beck,
Targeted inactivation of Npt2 in mice leads to severe renal phosphate wasting, hypercalciuria, and skeletal abnormalities.
1998, Pubmed
Beck,
Targeted inactivation of Npt2 in mice leads to severe renal phosphate wasting, hypercalciuria, and skeletal abnormalities.
1998,
Pubmed
Bergwitz,
SLC34A3 mutations in patients with hereditary hypophosphatemic rickets with hypercalciuria predict a key role for the sodium-phosphate cotransporter NaPi-IIc in maintaining phosphate homeostasis.
2006,
Pubmed
Bergwitz,
Hereditary hypophosphatemic rickets with hypercalciuria: pathophysiology, clinical presentation, diagnosis and therapy.
2019,
Pubmed
Block,
Phosphate homeostasis in CKD: report of a scientific symposium sponsored by the National Kidney Foundation.
2013,
Pubmed
Clark,
Protein-DNA Interactions at the Opossum Npt2a Promoter are Dependent upon NHERF-1.
2016,
Pubmed
Courbebaisse,
A new human NHERF1 mutation decreases renal phosphate transporter NPT2a expression by a PTH-independent mechanism.
2012,
Pubmed
,
Xenbase
Dinour,
Loss of function of NaPiIIa causes nephrocalcinosis and possibly kidney insufficiency.
2016,
Pubmed
,
Xenbase
Eshbach,
The transcriptome of the Didelphis virginiana opossum kidney OK proximal tubule cell line.
2017,
Pubmed
Evans,
Normal organ weights, serum chemistry, hematology, and cecal and nasopharyngeal bacterial cultures in the gray short-tailed opossum (Monodelphis domestica).
2010,
Pubmed
GTEx Consortium,
The Genotype-Tissue Expression (GTEx) project.
2013,
Pubmed
Haito-Sugino,
Processing and stability of type IIc sodium-dependent phosphate cotransporter mutations in patients with hereditary hypophosphatemic rickets with hypercalciuria.
2012,
Pubmed
,
Xenbase
Hernando,
PDZ-domain interactions and apical expression of type IIa Na/P(i) cotransporters.
2002,
Pubmed
Ito,
Interaction of a farnesylated protein with renal type IIa Na/Pi co-transporter in response to parathyroid hormone and dietary phosphate.
2004,
Pubmed
Ito,
An apical expression signal of the renal type IIc Na+-dependent phosphate cotransporter in renal epithelial cells.
2010,
Pubmed
Jones,
Hereditary hypophosphatemic rickets with hypercalciuria is not caused by mutations in the Na/Pi cotransporter NPT2 gene.
2001,
Pubmed
Karim,
NHERF1 mutations and responsiveness of renal parathyroid hormone.
2008,
Pubmed
Katai,
Acute regulation by dietary phosphate of the sodium-dependent phosphate transporter (NaP(i)-2) in rat kidney.
1997,
Pubmed
Kimura,
Localization of particulate guanylate cyclase in plasma membranes and microsomes of rat liver.
1975,
Pubmed
Koyama,
Establishment and characterization of a cell line from the American opossum (Didelphys virginiana).
1978,
Pubmed
Kuro-o,
A potential link between phosphate and aging--lessons from Klotho-deficient mice.
2010,
Pubmed
Lorenz-Depiereux,
Hereditary hypophosphatemic rickets with hypercalciuria is caused by mutations in the sodium-phosphate cotransporter gene SLC34A3.
2006,
Pubmed
Mahon,
Na+/H+ exchanger-regulatory factor 1 mediates inhibition of phosphate transport by parathyroid hormone and second messengers by acting at multiple sites in opossum kidney cells.
2003,
Pubmed
Miyamoto,
Sodium-dependent phosphate cotransporters: lessons from gene knockout and mutation studies.
2011,
Pubmed
Myakala,
Renal-specific and inducible depletion of NaPi-IIc/Slc34a3, the cotransporter mutated in HHRH, does not affect phosphate or calcium homeostasis in mice.
2014,
Pubmed
Nishimura,
Tissue-specific mRNA expression profiles of human solute carrier transporter superfamilies.
2008,
Pubmed
Ohkido,
Cloning, gene structure and dietary regulation of the type-IIc Na/Pi cotransporter in the mouse kidney.
2003,
Pubmed
,
Xenbase
Prié,
Nephrolithiasis and osteoporosis associated with hypophosphatemia caused by mutations in the type 2a sodium-phosphate cotransporter.
2002,
Pubmed
,
Xenbase
Rajagopal,
Exome sequencing identifies a novel homozygous mutation in the phosphate transporter SLC34A1 in hypophosphatemia and nephrocalcinosis.
2014,
Pubmed
Schlingmann,
Autosomal-Recessive Mutations in SLC34A1 Encoding Sodium-Phosphate Cotransporter 2A Cause Idiopathic Infantile Hypercalcemia.
2016,
Pubmed
,
Xenbase
Scotto-Lavino,
3' end cDNA amplification using classic RACE.
2006,
Pubmed
Segawa,
Growth-related renal type II Na/Pi cotransporter.
2002,
Pubmed
,
Xenbase
Segawa,
Type IIc sodium-dependent phosphate transporter regulates calcium metabolism.
2009,
Pubmed
Segawa,
Npt2a and Npt2c in mice play distinct and synergistic roles in inorganic phosphate metabolism and skeletal development.
2009,
Pubmed
Su,
Cell confluence-induced activation of signal transducer and activator of transcription-3 (Stat3) triggers epithelial dome formation via augmentation of sodium hydrogen exchanger-3 (NHE3) expression.
2007,
Pubmed
Tieder,
Hereditary hypophosphatemic rickets with hypercalciuria.
1985,
Pubmed
Vervloet,
The role of phosphate in kidney disease.
2017,
Pubmed
Wagner,
The SLC34 family of sodium-dependent phosphate transporters.
2014,
Pubmed
Yamamoto,
Hereditary hypophosphatemic rickets with hypercalciuria: a study for the phosphate transporter gene type IIc and osteoblastic function.
2007,
Pubmed
