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同型二聚体驱动蛋白Kif17对脊椎动物光感受器感觉外段的发育至关重要。

The homodimeric kinesin, Kif17, is essential for vertebrate photoreceptor sensory outer segment development.

作者信息

Insinna Christine, Pathak Narendra, Perkins Brian, Drummond Iain, Besharse Joseph C

机构信息

Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, 8701 Watertown Plank Rd, Milwaukee, WI 53226, USA.

出版信息

Dev Biol. 2008 Apr 1;316(1):160-70. doi: 10.1016/j.ydbio.2008.01.025. Epub 2008 Jan 31.

Abstract

Sensory cilia and intraflagellar transport (IFT), a pathway essential for ciliogenesis, play important roles in embryonic development and cell differentiation. In vertebrate photoreceptors IFT is required for the early development of ciliated sensory outer segments (OS), an elaborate organelle that sequesters the many proteins comprising the phototransduction machinery. As in other cilia and flagella, heterotrimeric members of the kinesin 2 family have been implicated as the anterograde IFT motor in OS. However, in Caenorhabditis elegans, OSM-3, a homodimeric kinesin 2 motor, plays an essential role in some, but not all sensory cilia. Kif17, a vertebrate OSM-3 homologue, is known for its role in dendritic trafficking in neurons, but a function in ciliogenesis has not been determined. We show that in zebrafish Kif17 is widely expressed in the nervous system and retina. In photoreceptors Kif17 co-localizes with IFT proteins within the OS, and co-immunoprecipitates with IFT proteins. Knockdown of Kif17 has little if any effect in early embryogenesis, including the formation of motile sensory cilia in the pronephros. However, OS formation and targeting of the visual pigment protein is severely disrupted. Our analysis shows that Kif17 is essential for photoreceptor OS development, and suggests that Kif17 plays a cell type specific role in vertebrate ciliogenesis.

摘要

感觉纤毛和鞭毛内运输(IFT)是纤毛发生所必需的途径,在胚胎发育和细胞分化中起重要作用。在脊椎动物光感受器中,IFT是纤毛状感觉外段(OS)早期发育所必需的,OS是一种复杂的细胞器,它隔离了许多组成光转导机制的蛋白质。与其他纤毛和鞭毛一样,驱动蛋白2家族的异源三聚体成员被认为是OS中IFT的正向运动蛋白。然而,在秀丽隐杆线虫中,同型二聚体驱动蛋白2运动蛋白OSM-3在一些但不是所有的感觉纤毛中起重要作用。脊椎动物OSM-3同源物Kif17以其在神经元树突运输中的作用而闻名,但尚未确定其在纤毛发生中的功能。我们发现,在斑马鱼中,Kif17在神经系统和视网膜中广泛表达。在光感受器中,Kif17与OS内的IFT蛋白共定位,并与IFT蛋白进行免疫共沉淀。敲低Kif17对早期胚胎发育几乎没有影响,包括前肾中运动性感觉纤毛的形成。然而,OS的形成和视觉色素蛋白的靶向定位受到严重破坏。我们的分析表明,Kif17对光感受器OS的发育至关重要,并表明Kif17在脊椎动物纤毛发生中发挥细胞类型特异性作用。

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