title: Jouberin localizes to collecting ducts and interacts with nephrocystin-1.
abstract: Joubert syndrome and related disorders are autosomal recessive multisystem diseases characterized by cerebellar vermis aplasia/hypoplasia, retinal degeneration and cystic kidney disease. There are five known genes; mutations of which give rise to a spectrum of renal cystic diseases the most common of which is nephronophthisis, a disorder characterized by early loss of urinary concentrating ability, renal fibrosis, corticomedullary cyst formation and renal failure. Many of the proteins encoded by these genes interact with one another and are located at adherens junctions or the primary cilia and or basal bodies. Here we characterize Jouberin, a multi-domain protein encoded by the AHI1 gene. Immunohistochemistry with a novel antibody showed that endogenous Jouberin is expressed in brain, kidney and HEK293 cells. In the kidney, Jouberin co-localized with aquaporin-2 in the collecting ducts. We show that Jouberin interacts with nephrocystin-1 as determined by yeast-2-hybrid system and this was confirmed by exogenous and endogenous co-immunoprecipitation in HEK293 cells. Jouberin is expressed at cell-cell junctions, primary cilia and basal body of mIMCD3 cells while a Jouberin-GFP construct localized to centrosomes in subconfluent and dividing MDCK cells. Our results suggest that Jouberin is a protein whose expression pattern supports both the adherens junction and the ciliary hypotheses for abnormalities leading to nephronophthisis.
authors.affiliation: Institute of Human Genetics, International Centre for Life, Newcastle University, Newcastle Upon Tyne, UK.
authors.forename: Lorraine
authors.initials: L
authors.lastname: Eley
authors.forename: Christos
authors.initials: C
authors.lastname: Gabrielides
authors.forename: Matthew
authors.initials: M
authors.lastname: Adams
authors.forename: Colin A
authors.initials: CA
authors.lastname: Johnson
authors.forename: Friedhelm
authors.initials: F
authors.lastname: Hildebrandt
authors.forename: John A
authors.initials: JA
authors.lastname: Sayer
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D033942:Adaptor Proteins, Vesicular Transport; D000818:Animals; D051399:Aquaporin 2 / Q000378:metabolism; D002460:Cell Line; D018385:Centrosome / Q000737:chemistry; D002923:Cilia / Q000737:chemistry; D003598:Cytoskeletal Proteins; D004285:Dogs; D006801:Humans; D007150:Immunohistochemistry; D007365:Intercellular Junctions / Q000737:chemistry; D007685:Kidney Tubules, Collecting / Q000737:chemistry* / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D011485:Protein Binding; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: C487178:AHI1 protein, human; D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; C465818:Ahi1 protein, mouse; D051399:Aquaporin 2; D003598:Cytoskeletal Proteins; D008565:Membrane Proteins; C108725:NPHP1 protein, human; D011518:Proto-Oncogene Proteins