Article

Essential role of nephrocystin in photoreceptor intraflagellar transport in mouse.

Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan, Republic of China.
Human Molecular Genetics (impact factor: 7.64). 03/2009; 18(9):1566-77. DOI:10.1093/hmg/ddp068
Source: PubMed

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.

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Keywords

analogous structure
 
cargo molecules
 
ciliary transition zone
 
cilium assembly
 
cilium axoneme
 
common epithelial cells
 
connecting cilia
 
EmGFP-tagged nephrocystin
 
functional ciliary
 
IFT particle components
 
inter-segmental traffic
 
microtubule-based transport system
 
nephrocystin
 
Nephrocystin mutations account
 
Nphp1-targeted mutant mice
 
outer segments
 
retinal photoreceptors
 
transgenic mice
 
transportation efficiency
 
vast majority