title: Caenorhabditis elegans ciliary protein NPHP-8, the homologue of human RPGRIP1L, is required for ciliogenesis and chemosensation.
abstract: Nephronophthisis (NPHP) is the most frequent genetic cause of end-stage renal failure in children and young adults. NPHP8/RPGRIP1L is a novel ciliary gene that, when mutated, in addition to causing NPHP, also causes Joubert syndrome (JBTS) and Meckel syndrome (MKS). The exact function of NPHP8 and how defects in NPHP8 lead to human diseases are poorly understood. Here, we studied the Caenorhabditis elegans homolog nphp-8 (C09G5.8) and explored the possible function of NPHP-8 in ciliated sensory neurons. We determined the gene structure of nphp-8 through rapid amplification of cDNA ends (RACE) analysis and discovered an X-box motif that had been previously overlooked. Moreover, NPHP-8 co-localized with NPHP-4 at the transition zone at the base of cilia. Mutation of nphp-8 led to abnormal dye filling (Dyf) and shorter cilia lengths in a subset of ciliary neurons. In addition, chemotaxis to several volatile attractants was significantly impaired in nphp-8 mutants. Our data suggest that NPHP-8/RPGRIP1L plays an important role in cilia formation and cilia-mediated chemosensation in a cell type-specific manner.
authors.affiliation: Joint Laboratory of the Institute of Biophysics & Huazhong University of Science and Technology, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, PR China.
authors.forename: Lin
authors.initials: L
authors.lastname: Liu
authors.forename: Mingshu
authors.initials: M
authors.lastname: Zhang
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Xia
authors.forename: Pingyong
authors.initials: P
authors.lastname: Xu
authors.forename: Liangyi
authors.initials: L
authors.lastname: Chen
authors.forename: Tao
authors.initials: T
authors.lastname: Xu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000502:physiology; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002633:Chemotaxis; D002923:Cilia / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D006801:Humans; D052177:Kidney Diseases, Cystic / Q000151:congenital / Q000235:genetics; D009154:Mutation; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D011506:Proteins; C532826:RPGRIP1L protein, human