title: Inv acts as a molecular anchor for Nphp3 and Nek8 in the proximal segment of primary cilia.
abstract: A primary cilium is an antenna-like structure extending from the surface of most vertebrate cells. It is structurally divided along its vertical axis into sub-compartments that include the ciliary tip, the shaft, the ciliary necklace segment, the transitional zone and the basal body. We recently discovered that the shaft of the primary cilia has a distinct molecular compartment, termed the "Inv compartment", which is characterized by the accumulation of Inv at the base of primary cilia. Inv was discovered as a causative gene in inv mutant mice. It was later found to be responsible for the infantile type of nephronophthisis (NPHP2). Nephronophthisis (NPHP) is an autosomal recessive kidney disease. Nine causative genes have been identified, with all examined products thought to function in cilia, basal body and/or centrioles. However, their exact intra-ciliary localization and relationship have not been clear. Here, we report that products of Nphp3 and Nek8 (the mouse orthologs of the causative genes for NPHP3 and NPHP9, respectively) localize to the Inv compartment. We also show that Inv is essential for the compartmental localization of Nphp3 and Nek8, whereas localization of Inv does not require Nphp3 or Nek8. Nphp1 and Nphp4 also localize at the proximal region of the cilium, but not in Inv compartment. Our results indicate that Inv acts as an anchor for Nphp3 and Nek8 in the Inv compartment, and suggest that Inv compartment is a candidate site for intra-ciliary interaction of Inv, Nphp3 and Nek8.
authors.affiliation: Department of Anatomy and Developmental Biology, Kyoto Prefectural University of Medicine, Japan.
authors.forename: Dai
authors.initials: D
authors.lastname: Shiba
authors.forename: Danielle K
authors.initials: DK
authors.lastname: Manning
authors.forename: Hisashi
authors.initials: H
authors.lastname: Koga
authors.forename: David R
authors.initials: DR
authors.lastname: Beier
authors.forename: Takahiko
authors.initials: T
authors.lastname: Yokoyama
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D002923:Cilia / Q000378:metabolism*; D003598:Cytoskeletal Proteins; D016547:Kinesins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008856:Microscopy, Fluorescence; D000072379:NIMA-Related Kinases; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; C491947:Invs protein, mouse; C534985:Nphp1 protein, mouse; D014157:Transcription Factors; D011494:Protein Kinases; D000072379:NIMA-Related Kinases; C499219:Nek8 protein, mouse; D017346:Protein Serine-Threonine Kinases; C528698:nephrocystin-3, mouse; D016547:Kinesins