Abstract
Anterograde intraflagellar transport (IFT) employing kinesin-2 molecular motors has been implicated in trafficking of photoreceptor outer segment proteins. We generated embryonic retina-specific (prefix "emb") and adult tamoxifen-induced (prefix "tam") deletions of KIF3a and IFT88 in adult mice to study photoreceptor ciliogenesis and protein trafficking. In (emb)Kif3a(-/-) and in (emb)Ift88(-/-) mice, basal bodies failed to extend transition zones (connecting cilia) with outer segments, and visual pigments mistrafficked. In contrast, (tam)Kif3a(-/-) and (tam)Ift88(-/-) photoreceptor axonemes disintegrated slowly post-induction, starting distally, but rhodopsin and cone pigments trafficked normally for more than 2 weeks, a time interval during which the outer segment is completely renewed. The results demonstrate that visual pigments transport to the retinal outer segment despite removal of KIF3 and IFT88, and KIF3-mediated anterograde IFT is responsible for photoreceptor transition zone and axoneme formation.
Highlights
Heterotrimeric kinesin-2 (KIF3) has been implicated in intraflagellar trafficking of photoreceptor membrane proteins by intraflagellar transport (IFT)
Under control of the Six3 promoter, Cre is expressed in mouse neuroretina progenitors as early as embryonic day 9.5 [37]; KIF3A is expected to be deleted before photoreceptor differentiation in MAY 15, 2015
Our results show that deletion of KIF3A or IFT88 in retinal progenitors prevented photoreceptor
Summary
Heterotrimeric kinesin-2 (KIF3) has been implicated in intraflagellar trafficking of photoreceptor membrane proteins by IFT. Results: KIF3 and IFT88 are required for transition zone and axoneme formation, but are dispensable for rhodopsin trafficking. Anterograde intraflagellar transport (IFT) employing kinesin-2 molecular motors has been implicated in trafficking of photoreceptor outer segment proteins. In embKif3a؊/؊ and in embIft88؊/؊ mice, basal bodies failed to extend transition zones (connecting cilia) with outer segments, and visual pigments mistrafficked. The results demonstrate that visual pigments transport to the retinal outer segment despite removal of KIF3 and IFT88, and KIF3-mediated anterograde IFT is responsible for photoreceptor transition zone and axoneme formation. Retina-specific deletion of either KIF3A or IFT88 during early development resulted in failure to form PTZs; depletion of either KIF3A or IFT88 by tamoxifen induction resulted in progressive, distal shortening of the OS axoneme, despite continued rhodopsin trafficking for at least 10 days. Our data indicate that the phenotype of KIF3 loss strongly depends on the time of Credriven recombination, and that KIF3-driven IFT functions primarily in photoreceptor ciliogenesis, PTZ formation, and axoneme stabilization
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