Human Molecular Genetics Advance Access originally published online on February 9, 2009
Human Molecular Genetics 2009 18(9):1566-1577; doi:10.1093/hmg/ddp068
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Essential role of nephrocystin in photoreceptor intraflagellar transport in mouse
1 Institute of Molecular Biology, Academia Sinica, Taipei 11529, Taiwan, Republic of China 2 Department of Pediatrics, Institute of Clinical Medicine, National Cheng Kung University Medical Center, Tainan 704, Taiwan, Republic of China 3 Department of Life Sciences, National Taiwan Normal University, Taipei 106, Taiwan, Republic of China and 4 Department of Neurology, Center for Neuropsychiatry, China Medical University and Hospital, Taichung 404, Taiwan, Republic of China
* To whom correspondence should be addressed at. Tel: +886 02 27899312; Fax: +886 02 27826085; Email: stjiang{at}imb.sinica.edu.tw
Received December 15, 2008; Accepted February 4, 2009
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.
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