|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
8
|
|
pubmed:dateCreated |
2005-7-21
|
|
pubmed:abstractText |
Megalin is a multifunctional endocytic receptor that is expressed in renal proximal tubules and plays critical roles in the renal uptake of various proteins. It was hypothesized that megalin-dependent endocytosis might play a role in renal phosphate reabsorption. For addressing the short-term effects of altered megalin function, a recombinant protein for the soluble form of 39-kD receptor-associated protein (RAP) was administered intraperitoneally to 7-wk-old mice. Histidine (His)-tagged soluble RAP (amino acids 39 to 356) lacking the amino-terminal signal peptide and the carboxy-terminal endoplasmic reticulum retention signal was prepared by bacterial expression (designated His-sRAP). After the direct interaction between His-sRAP and megalin was confirmed, mice were given a single intraperitoneal administration of His-sRAP (3.5 mg/dose). Immunostaining and Western blot analyses demonstrated the uptake of His-sRAP and the accelerated internalization of megalin in proximal tubular cells 1 h after administration. In addition, internalization of the type II sodium/phosphate co-transporter (NaPi-II) was observed. The effects of three sequential administrations of His-sRAP (3.5 mg/dose, three doses at 4-h intervals) then were examined, and increased urinary excretion of low molecular weight proteins, including vitamin D-binding protein, was found, which is consistent with findings reported for megalin-deficient mice. It is interesting that urinary excretion of phosphate was also increased, and the protein level of NaPi-II in the brush border membrane was decreased. Serum concentration of 25-hydroxyvitamin D was decreased, whereas the plasma level of intact parathyroid hormone was not altered by the administration of His-sRAP. The results suggest that the His-sRAP-induced acceleration of megalin-mediated endocytosis caused phosphaturia via altered subcellular distribution of NaPi-II.
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Histidine,
http://linkedlifedata.com/resource/pubmed/chemical/LDL-Receptor Related...,
http://linkedlifedata.com/resource/pubmed/chemical/Ligands,
http://linkedlifedata.com/resource/pubmed/chemical/Low Density Lipoprotein...,
http://linkedlifedata.com/resource/pubmed/chemical/Parathyroid Hormone,
http://linkedlifedata.com/resource/pubmed/chemical/Phosphates,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Sorting Signals,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Slc34a1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Sodium-Phosphate Cotransporter...,
http://linkedlifedata.com/resource/pubmed/chemical/Sodium-Phosphate Cotransporter...,
http://linkedlifedata.com/resource/pubmed/chemical/Symporters,
http://linkedlifedata.com/resource/pubmed/chemical/Vitamin D-Binding Protein
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Aug
|
|
pubmed:issn |
1046-6673
|
|
pubmed:author |
|
|
pubmed:issnType |
Print
|
|
pubmed:volume |
16
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
2338-45
|
|
pubmed:dateRevised |
2011-11-17
|
|
pubmed:meshHeading |
pubmed-meshheading:15976002-Animals,
pubmed-meshheading:15976002-Blotting, Western,
pubmed-meshheading:15976002-Electrophoresis, Polyacrylamide Gel,
pubmed-meshheading:15976002-Endocytosis,
pubmed-meshheading:15976002-Endoplasmic Reticulum,
pubmed-meshheading:15976002-Histidine,
pubmed-meshheading:15976002-Infusions, Parenteral,
pubmed-meshheading:15976002-Kidney,
pubmed-meshheading:15976002-Kidney Tubules,
pubmed-meshheading:15976002-LDL-Receptor Related Protein-Associated Protein,
pubmed-meshheading:15976002-Ligands,
pubmed-meshheading:15976002-Low Density Lipoprotein Receptor-Related Protein-2,
pubmed-meshheading:15976002-Male,
pubmed-meshheading:15976002-Mice,
pubmed-meshheading:15976002-Mice, Inbred ICR,
pubmed-meshheading:15976002-Microscopy, Fluorescence,
pubmed-meshheading:15976002-Microvilli,
pubmed-meshheading:15976002-Parathyroid Hormone,
pubmed-meshheading:15976002-Phosphates,
pubmed-meshheading:15976002-Protein Binding,
pubmed-meshheading:15976002-Protein Sorting Signals,
pubmed-meshheading:15976002-Protein Structure, Tertiary,
pubmed-meshheading:15976002-Recombinant Proteins,
pubmed-meshheading:15976002-Sodium-Phosphate Cotransporter Proteins,
pubmed-meshheading:15976002-Sodium-Phosphate Cotransporter Proteins, Type IIa,
pubmed-meshheading:15976002-Symporters,
pubmed-meshheading:15976002-Time Factors,
pubmed-meshheading:15976002-Vitamin D-Binding Protein
|
|
pubmed:year |
2005
|
|
pubmed:articleTitle |
Intraperitoneal administration of recombinant receptor-associated protein causes phosphaturia via an alteration in subcellular distribution of the renal sodium phosphate co-transporter.
|
|
pubmed:affiliation |
Department of Environmental Medicine, Osaka Medical Center and Research Institute for Maternal and Child Health, 840 Murodo-cho, Izumi, Osaka 594-1101, Japan.
|
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|
