title: Anks3 interacts with nephronophthisis proteins and is required for normal renal development.
abstract: Nephronophthisis (NPH) is a heterogenetic autosomal recessive disorder associated with kidney cysts and multiple extrarenal manifestations. The disease-associated gene products (NPHPs) typically contain domains involved in protein-protein interactions, and appear to exert their tissue-specific functions in large protein complexes. Most NPHPs localize to the cilium and/or basal body; however, their precise molecular functions remain largely unknown. We have recently identified the SAM-domain containing protein Anks3 as a potential ANKS6/NPHP16-interacting protein, and report now that Anks3 interacts with several NPHPs as well as with Bicc1 and the oxygen-sensitive asparaginyl hydroxylase HIF1AN. Knockdown of anks3 in zebrafish embryos was associated with NPH-typical manifestations, including ciliary abnormalities, cyst formation, and laterality defects. In multi-ciliated epidermal cells, GFP-tagged Anks3 localizes to the cilium, but forms large aggregates in the absence of NPHP1, indicating that the negatively charged NPHP1 curtails the polymerization of Anks3. Collectively, these findings suggest that Anks3 is a cilia-associated molecule that partners with the ANKS6- and via NPHP1 to the NPHP1-4-8 module. Thus, developmental defects associated with Anks3 depletion in zebrafish suggest that ANKS3 mutations may cause NPH or NPH-like disease in humans.
authors: Renal Division, Department of Medicine, University Freiburg Medical Center, Freiburg, Germany.
authors: Toma A
authors: TA
authors: Yakulov
authors: Renal Division, Department of Medicine, University Freiburg Medical Center, Freiburg, Germany.
authors: Takayuki
authors: T
authors: Yasunaga
authors: Renal Division, Department of Medicine, University Freiburg Medical Center, Freiburg, Germany.
authors: Haribaskar
authors: H
authors: Ramachandran
authors: Renal Division, Department of Medicine, University Freiburg Medical Center, Freiburg, Germany.
authors: Christina
authors: C
authors: Engel
authors: Renal Division, Department of Medicine, University Freiburg Medical Center, Freiburg, Germany.
authors: Barbara
authors: B
authors: Müller
authors: Renal Division, Department of Medicine, University Freiburg Medical Center, Freiburg, Germany.
authors: Sylvia
authors: S
authors: Hoff
authors: 1] Department of Dermatology, University Freiburg Medical Center and Center of Biological Systems Analysis (ZBSA), Freiburg, Germany [2] Center for Biological Signaling Studies (BIOSS), Freiburg, Germany.
authors: Jörn
authors: J
authors: Dengjel
authors: 1] Renal Division, Department of Medicine, University Freiburg Medical Center, Freiburg, Germany [2] Center for Biological Signaling Studies (BIOSS), Freiburg, Germany.
authors: Soeren S
authors: SS
authors: Lienkamp
authors: 1] Renal Division, Department of Medicine, University Freiburg Medical Center, Freiburg, Germany [2] Center for Biological Signaling Studies (BIOSS), Freiburg, Germany.
authors: Gerd
authors: G
authors: Walz
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism*; D002923:Cilia / Q000378:metabolism; D003598:Cytoskeletal Proteins; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006801:Humans; D007668:Kidney / Q000002:abnormalities / Q000196:embryology*; D052177:Kidney Diseases, Cystic / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D006899:Mixed Function Oxygenases / Q000378:metabolism; D000072379:NIMA-Related Kinases; D009687:Nuclear Proteins / Q000378:metabolism; D058105:Polymerization; D011494:Protein Kinases / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D012857:Situs Inversus / Q000235:genetics; D014981:Xenopus; D029867:Xenopus Proteins / Q000235:genetics / Q000378:metabolism*; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: C000595708:ANKS3 protein, human; C000605319:ANKS3 protein, zebrafish; C532258:ANKS6 protein, human; D048868:Adaptor Proteins, Signal Transducing; C571508:Bicc1 protein, human; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D008565:Membrane Proteins; C108725:NPHP1 protein, human; C491578:NPHP4 protein, human; D009687:Nuclear Proteins; D011506:Proteins; D016601:RNA-Binding Proteins; C532826:RPGRIP1L protein, human; D012097:Repressor Proteins; D029867:Xenopus Proteins; D029961:Zebrafish Proteins; D006899:Mixed Function Oxygenases; C439790:HIF1AN protein, human; D011494:Protein Kinases; C458529:NEK8 protein, human; D000072379:NIMA-Related Kinases