title: Essential role of nephrocystin in photoreceptor intraflagellar transport in mouse.
abstract: Nephrocystin mutations account for the vast majority of juvenile nephronophthisis, the most common inherited cause of renal failure in children. Nephrocystin has been localized to the ciliary transition zone of epithelial cells or its analogous structure, connecting cilium of retinal photoreceptors. Thus, the retinal degeneration associated with nephronophthisis may be explained by a functional ciliary defect. However, the function of nephrocystin in cilium assembly and maintenance of common epithelial cells and photoreceptors is still obscure. Here, we used Nphp1-targeted mutant mice and transgenic mice expressing EmGFP-tagged nephrocystin to demonstrate that nephrocystin located at connecting cilium axoneme can affect the sorting mechanism and transportation efficiency of the traffic machinery between inner and outer segments of photoreceptors. This traffic machinery is now recognized as intraflagellar transport (IFT); a microtubule-based transport system consisting of motors, IFT particles and associated cargo molecules. Nephrocystin seems to control some of the IFT particle components moving along the connecting cilia so as to regulate this inter-segmental traffic. Our novel findings provide a clue to unraveling the regulatory mechanism of nephrocystin in IFT machinery.
authors.affiliation: Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan, Republic of China. stjiang@imb.sinica.edu.tw
authors.forename: Si-Tse
authors.initials: ST
authors.lastname: Jiang
authors.forename: Yuan-Yow
authors.initials: YY
authors.lastname: Chiou
authors.forename: Ellian
authors.initials: E
authors.lastname: Wang
authors.forename: Yi-Lin
authors.initials: YL
authors.lastname: Chien
authors.forename: Hua-Hui
authors.initials: HH
authors.lastname: Ho
authors.forename: Fang-Ju
authors.initials: FJ
authors.lastname: Tsai
authors.forename: Chun-Yu
authors.initials: CY
authors.lastname: Lin
authors.forename: Shu-Ping
authors.initials: SP
authors.lastname: Tsai
authors.forename: Hung
authors.initials: H
authors.lastname: Li
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002923:Cilia / Q000378:metabolism*; D003598:Cytoskeletal Proteins; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020419:Photoreceptor Cells, Vertebrate / Q000378:metabolism*; D021381:Protein Transport; D012162:Retinal Degeneration / Q000235:genetics / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; C534985:Nphp1 protein, mouse