title: Localization of Inv in a distinctive intraciliary compartment requires the C-terminal ninein-homolog-containing region.
abstract: The primary cilium is an antenna-like structure extending from the surface of most vertebrate cells. Loss or mutation of ciliary proteins can lead to polycystic kidney disease and other developmental abnormalities. inv mutant mice develop multiple renal cysts and are a model for human nephronophthisis type 2. The mouse Inv gene encodes a 1062-amino-acid protein that is localized in primary cilia. In this study, we show that the Inv protein (also known as inversin) is localized at a distinctive proximal segment of the primary cilium, using GFP-tagged Inv constructs and anti-Inv antibody. We named this segment the Inv compartment of the cilium. Further investigation of the Inv protein showed that 60 amino acids at its C-terminal, which contains ninein homologous sequences, are crucial for its localization to the Inv compartment. Fluorescence recovery after photobleaching analysis revealed that the Inv protein was dynamic within this compartment. These results suggest that localization of the Inv protein to the Inv compartment is actively regulated. The present study revealed that the primary cilium has a distinct molecular compartment in the body of the primary cilium with a specific confining and trafficking machinery that has not been detected previously by morphological examination.
authors.affiliation: Department of Anatomy and Developmental Biology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan.
authors.forename: Dai
authors.initials: D
authors.lastname: Shiba
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Yamaoka
authors.forename: Haruo
authors.initials: H
authors.lastname: Hagiwara
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Takamatsu
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hamada
authors.forename: Takahiko
authors.initials: T
authors.lastname: Yokoyama
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002923:Cilia / Q000378:metabolism / Q000648:ultrastructure; D036681:Fluorescence Recovery After Photobleaching; D006801:Humans; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D007690:Polycystic Kidney Diseases / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D015398:Signal Transduction / Q000502:physiology; D014157:Transcription Factors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
chemical_list: C491947:Invs protein, mouse; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors