Abstract
Defects in the cilium, a once thought vestigial organelle, have recently been implicated in many human diseases, including a number of cystic kidney diseases such as polycystic kidney disease (PKD), Bardet Bieldl Syndrome, and Meckel-Gruber Syndrome. In a forward genetic screen, qilin was identified as a novel gene important in the pathogenesis of kidney cysts in zebrafish. In this paper we characterized qilinhi3959A mutant's phenotypes in detail, investigated cilia formation in this mutant and performed structural and functional analysis of the Qilin protein. Results reveal Qilin's essential role in cilia assembly and maintenance in multiple organs, including the kidney, the lateral line organ, and the outer segment of the photoreceptor cell. In addition, rescue experiments suggest that defective pronephric cilia correlate with the formation of kidney cysts in qilinhi3959A mutants. Further, genetic analysis suggests that qilin interacts with multiple intraflagellar transport (IFT) complex B genes, which is supported by the striking phenotypic similarities between qilinhi3959A and IFT complex B mutants. Finally, through deletion analysis we provide evidence that the well-conserved N-terminus and the coiled-coil domain of Qilin are both essential and sufficient for its function. Taken all the observations together, we propose that Qilin acts in a similar role as IFT complex B proteins in cilia assembly, maintenance and kidney development in zebrafish.
Highlights
The cilium, an organelle projecting from the cell surface, had long been believed to be vestigial in vertebrates; in the past decade it has been shown to play a critical role in both vertebrate physiology and development
Qilin in vertebrate cilia biogenesis and maintenance Qilin is a novel protein we isolated in a previous genetic screen for cystic kidney mutants in zebrafish [12]
Dyf-3 transcription is regulated by DAF-19, a transcription factor that regulates multiple ciliary genes in C. elegans [29,30]
Summary
The cilium, an organelle projecting from the cell surface, had long been believed to be vestigial in vertebrates; in the past decade it has been shown to play a critical role in both vertebrate physiology and development. First identified in the green algae Chlamydomonas, IFT particles are multi-protein complexes believed to carry cargos essential for cilia biogenesis, maintenance and signaling [13,14]. They are composed of complex A and complex B subunits, with complex A more associated with retrograde transport [15,16] and complex B involved in anterograde transport [13,17]. Dyf-3 mutants develop truncated sensory cilia, suggesting that dyf-3 plays a role in cilia formation or maintenance in C. elegans [19,21]. N N-terminal and coiled-coil domains of Qilin are essential and sufficient for its functions
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
