Heterotrimeric Kinesin-2 (KIF3) Mediates Transition Zone and Axoneme Formation of Mouse Photoreceptors
Heterotrimeric Kinesin-2 (KIF3) Mediates Transition Zone and Axoneme Formation of Mouse Photoreceptors
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DOI：
10.1074/jbc.m115.638437
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发表时间：
2015-05-15
影响因子：
4.8
通讯作者：
Baehr, Wolfgang
中科院分区：
文献类型：
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作者：
Jiang, Li;Wei, Yuxiao;Baehr, Wolfgang
利用驱动蛋白-2分子马达的顺行鞭毛内运输（IFT）与光感受器外段蛋白的运输有关。我们在成年小鼠中产生胚胎视网膜特异性（前缀“emb”）和成年他莫昔芬诱导的KIF3a和IFT88缺失（前缀“tam”），以研究光感受器纤毛发生和蛋白质运输。在（emb）Kif3a（-/-）和（emb）Ift88（-/-）小鼠中，基底体无法延伸过渡区（连接纤毛）与外节，并且视觉色素误用。相比之下，（tam）Kif3a（-/-）和（tam）Ift88（-/-）光感受器轴突在诱导后缓慢分解，从远端开始，但视紫红质和视锥色素的正常运输超过2周，在此期间外段完全更新。结果表明，尽管去除KIF3和IFT88，视觉色素仍可运输到视网膜外节，KIF3介导的顺行IFT负责光感受器过渡区和轴突形成。
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.