title: Kidney injury molecule 1 (Kim1) is a novel ciliary molecule and interactor of polycystin 2.
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.affiliation: Renal Division, University Hospital Freiburg, Hugstetter Strasse 55, D-79106 Freiburg, Germany.
authors.forename: E Wolfgang
authors.initials: EW
authors.lastname: Kuehn
authors.forename: Marc N
authors.initials: MN
authors.lastname: Hirt
authors.forename: Anne-K
authors.initials: AK
authors.lastname: John
authors.forename: Petra
authors.initials: P
authors.lastname: Muehlenhardt
authors.forename: Christopher
authors.initials: C
authors.lastname: Boehlke
authors.forename: Michael
authors.initials: M
authors.lastname: Pütz
authors.forename: Albrecht G
authors.initials: AG
authors.lastname: Kramer-Zucker
authors.forename: Mikhail
authors.initials: M
authors.lastname: Bashkurov
authors.forename: Philipp S
authors.initials: PS
authors.lastname: van de Weyer
authors.forename: Fruzsina
authors.initials: F
authors.lastname: Kotsis
authors.forename: Gerd
authors.initials: G
authors.lastname: Walz
mesh_terms: D002460:Cell Line; D002923:Cilia / Q000378:metabolism; D000072596:Hepatitis A Virus Cellular Receptor 1; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D011991:Receptors, Virus / Q000235:genetics / Q000378:metabolism*; D050396:TRPP Cation Channels / Q000378:metabolism*; D014443:Tyrosine / Q000235:genetics / Q000378:metabolism
chemical_list: D000072596:Hepatitis A Virus Cellular Receptor 1; D008562:Membrane Glycoproteins; D011991:Receptors, Virus; D050396:TRPP Cation Channels; D014443:Tyrosine; C491143:HAVCR1 protein, human