|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
53
|
|
pubmed:dateCreated |
2004-12-23
|
|
pubmed:abstractText |
Constitutive albumin uptake by the proximal tubule is achieved by a receptor-mediated process in which the Cl(-) channel, ClC-5, plays an obligate role. Here we investigated the functional interaction between ClC-5 and ubiquitin ligases Nedd4 and Nedd4-2 and their role in albumin uptake in opossum kidney proximal tubule (OK) cells. In vivo immunoprecipitation using an anti-HECT antibody demonstrated that ClC-5 bound to ubiquitin ligases, whereas glutathione S-transferase pull-downs confirmed that the C terminus of ClC-5 bound both Nedd4 and Nedd4-2. Nedd4-2 alone was able to alter ClC-5 currents in Xenopus oocytes by decreasing cell surface expression of ClC-5. In OK cells, a physiological concentration of albumin (10 mug/ml) rapidly increased cell surface expression of ClC-5, which was also accompanied by the ubiquitination of ClC-5. Albumin uptake was reduced by inhibiting either the lysosome or proteasome. Total levels of Nedd4-2 and proteasome activity also increased rapidly in response to albumin. Overexpression of ligase defective Nedd4-2 or knockdown of endogenous Nedd4-2 with small interfering RNA resulted in significant decreases in albumin uptake. In contrast, pathophysiological concentrations of albumin (100 and 1000 mug/ml) reduced the levels of ClC-5 and Nedd4-2 and the activity of the proteasome to the levels seen in the absence of albumin. These data demonstrate that normal constitutive uptake of albumin by the proximal tubule requires Nedd4-2, which may act via ubiquitination to shunt ClC-5 into the endocytic pathway.
|
|
pubmed:grant |
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Albumins,
http://linkedlifedata.com/resource/pubmed/chemical/CLC-5 chloride channel,
http://linkedlifedata.com/resource/pubmed/chemical/Chloride Channels,
http://linkedlifedata.com/resource/pubmed/chemical/Endosomal Sorting Complexes...,
http://linkedlifedata.com/resource/pubmed/chemical/Glutathione Transferase,
http://linkedlifedata.com/resource/pubmed/chemical/Nedd4 ubiquitin protein ligases,
http://linkedlifedata.com/resource/pubmed/chemical/Proteasome Endopeptidase Complex,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering,
http://linkedlifedata.com/resource/pubmed/chemical/Ubiquitin,
http://linkedlifedata.com/resource/pubmed/chemical/Ubiquitin-Protein Ligases
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Dec
|
|
pubmed:issn |
0021-9258
|
|
pubmed:author |
|
|
pubmed:issnType |
Print
|
|
pubmed:day |
31
|
|
pubmed:volume |
279
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
54996-5007
|
|
pubmed:dateRevised |
2009-11-19
|
|
pubmed:meshHeading |
pubmed-meshheading:15489223-Albumins,
pubmed-meshheading:15489223-Animals,
pubmed-meshheading:15489223-Biotinylation,
pubmed-meshheading:15489223-Blotting, Western,
pubmed-meshheading:15489223-Cell Line,
pubmed-meshheading:15489223-Cell Membrane,
pubmed-meshheading:15489223-Chloride Channels,
pubmed-meshheading:15489223-Dose-Response Relationship, Drug,
pubmed-meshheading:15489223-Endocytosis,
pubmed-meshheading:15489223-Endosomal Sorting Complexes Required for Transport,
pubmed-meshheading:15489223-Glutathione Transferase,
pubmed-meshheading:15489223-Immunoprecipitation,
pubmed-meshheading:15489223-Kidney Tubules,
pubmed-meshheading:15489223-Lysosomes,
pubmed-meshheading:15489223-Models, Biological,
pubmed-meshheading:15489223-Oocytes,
pubmed-meshheading:15489223-Opossums,
pubmed-meshheading:15489223-Proteasome Endopeptidase Complex,
pubmed-meshheading:15489223-Protein Binding,
pubmed-meshheading:15489223-RNA, Messenger,
pubmed-meshheading:15489223-RNA, Small Interfering,
pubmed-meshheading:15489223-Ubiquitin,
pubmed-meshheading:15489223-Ubiquitin-Protein Ligases,
pubmed-meshheading:15489223-Xenopus
|
|
pubmed:year |
2004
|
|
pubmed:articleTitle |
Nedd4-2 functionally interacts with ClC-5: involvement in constitutive albumin endocytosis in proximal tubule cells.
|
|
pubmed:affiliation |
School of Biomedical Sciences, The University of Queensland, Brisbane, Queensland 4072, Australia.
|
|
pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
|
