Abstract |
Inherited mutations in genes encoding for ciliary proteins lead to a broad spectrum of human diseases, such as polycystic kidney disease (PKD), situs inversus and retinitis pigmentosa. In the human kidney, autosomal dominant PKD ( ADPKD) is caused by mutations in PKD1 (PC1), or PKD2 (TRPP2). Both are necessary for ciliary mechanotransduction, whereby bending of the cilium elicits a calcium response in the cell. We have previously shown that overexpression of mutated forms of the chemosensor kidney injury molecule 1 (Kim1) abolishes the flow response in ciliated MDCK cells. Here we identify Kim1 as an endogenous ciliary protein. Kim1 co-precipitates with TRPP2. Mutational analysis reveals that the interaction between Kim1 and TRPP2 requires the ciliary sorting motif in the N-terminus of TRPP2, and the presence of a highly conserved tyrosine in the intracellular tail of Kim1, which has previously been shown to play a role in ciliary flow sensing. These data support the notion that TRPP2 functionally interacts with ciliary chemosensors.
|
Authors | E Wolfgang Kuehn, Marc N Hirt, Anne-K John, Petra Muehlenhardt, Christopher Boehlke, Michael Pütz, Albrecht G Kramer-Zucker, Mikhail Bashkurov, Philipp S van de Weyer, Fruzsina Kotsis, Gerd Walz |
Journal | Biochemical and biophysical research communications
(Biochem Biophys Res Commun)
Vol. 364
Issue 4
Pg. 861-6
(Dec 28 2007)
ISSN: 1090-2104 [Electronic] United States |
PMID | 18273441
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Chemical References |
- HAVCR1 protein, human
- Hepatitis A Virus Cellular Receptor 1
- Membrane Glycoproteins
- Receptors, Virus
- TRPP Cation Channels
- polycystic kidney disease 2 protein
- Tyrosine
|
Topics |
- Cell Line
- Cilia
(metabolism)
- Hepatitis A Virus Cellular Receptor 1
- Humans
- Membrane Glycoproteins
(genetics, metabolism)
- Phosphorylation
- Protein Binding
- Receptors, Virus
(genetics, metabolism)
- TRPP Cation Channels
(metabolism)
- Tyrosine
(genetics, metabolism)
|