Heterotrimeric Kinesin-2 (KIF3) Mediates Transition Zone and Axoneme Formation of Mouse Photoreceptors |
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Authors: | Li Jiang Yuxiao Wei Cecinio C Ronquillo Robert E Marc Bradley K Yoder Jeanne M Frederick Wolfgang Baehr |
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Institution: | From the Departments of ‡Ophthalmology and Visual Sciences and ;‖Neurobiology and Anatomy, University of Utah Health Science Center, Salt Lake City, Utah 84132, ;the §Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, Alabama 35294, and ;the ¶Department of Biology, University of Utah, Salt Lake City, Utah 84112 |
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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 embKif3a−/− and in embIft88−/− mice, basal bodies failed to extend transition zones (connecting cilia) with outer segments, and visual pigments mistrafficked. In contrast, tamKif3a−/− and tamIft88−/− 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. |
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Keywords: | cilia gene knockout homologous recombination photoreceptor retinal degeneration IFT88 KIF3A heterotrimeric kinesin-2 intraflagellar transport anterograde intraflagellar transport (IFT) conditional KIF3A knockout conditional IFT88 knockout |
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