Jiang Li will be delivering a seminar, Intraflagellar Transport (IFT) Essential For Photoreceptor Connecting Cilium/Axoneme Formation and Maintenance on Tuesday, August 19th, 2014 in the John A. Moran Eye Center auditorium.
A light-sensitive photoreceptor outer segment (OS) is a modified primary cilium and communicates with the inner segment (IS) through a “connecting cilium” (CC), a structure equivalent to the transition zone of primary cilia. Anterograde intraflagellar transport (IFT) has been implicated in protein trafficking of photoreceptor sensory cilia. IFT is a bidirectional ciliary trafficking pathway conserved between invertebrates and vertebrates with heterotrimeric (KIF3) and homodimeric (KIF17) kinesin-II as anterograde motors. To differentiate anterograde IFT func,on in photoreceptor development and survival, we generated embryonic retina-specific and postnatal tamoxifen-induced deletions of KIF3a, and germline deletions of KIF17. In embryonic retina-specific Kif3a knockout mouse, basal bodies docked to the cortex of mutant photoreceptors but failed to form CC and OS. Rhodopsin, cone pigments and other OS proteins were retained in the knockout photoreceptor IS. In contrast, tamoxifen- induced deletion of Kif3a in adult mouse led to slowly progressing photoreceptor degeneration due to the inability of photoreceptors to maintain their mature axonemes. Rhodopsin and cone pigments trafficked to OS up to 3 weeks post- induction. Once fully mature, the Kif3a knockout photoreceptor axonemes were unable to be maintained and disintegrated slowly. Germline deletion of KIF17 affected neither axoneme structure nor photoreceptor morphology/function, thereby excluding an essential role of KIF17 in photoreceptor IFT. Our results demonstrate that IFT is not required for rhodopsin transport to the OS. Rather, anterograde IFT mediated by KIF3a, but not by KIF17, participates in photoreceptor transition zone (PTZ)/axoneme formation and maintenance.