Functional coordination of intraflagellar transport motors
Functional coordination of intraflagellar transport motors
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DOI：
10.1038/nature03818
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发表时间：
2005-07-28
期刊：
影响因子：
64.8
通讯作者：
Scholey, JM
中科院分区：
文献类型：
--
作者：
Ou, GS;Blacque, OE;Scholey, JM
纤毛在运动和感觉接收中起着不同的作用，纤毛功能的缺陷导致了诸如Bardet-Biedl综合征(BBS)等纤毛疾病。鞭毛内转运(IFT)马达通过将纤毛前体结合到称为IFT颗粒的蛋白质复合体上，从纤毛底部到它们在远端末端的结合部位来组装和维持纤毛(1-3)。在秀丽线虫中，这是由两个IFT马达完成的，它们是Kinesin-II和渗透回避缺陷(OSM)-3 Kinesin，它们协同形成两个顺序的顺行IFT通路，建立纤毛的不同部分(4-7)。通过观察大量纤毛突变体的荧光IFT马达和IFT颗粒沿纤毛的运动，我们鉴定了三个基因，它们的蛋白产物介导了这些马达的功能协调。BBS蛋白BBS-7和BBS-8是稳定包含两个IFT发动机的IFT颗粒复合体所必需的，因为BBS-7和BBS-8突变体中的IFT颗粒分解成两个亚复合体IFT-A和IFT-B，这两个亚复合体分别由Kinesin-II和OSM-3 Kinesin移动。OSM-3动蛋白与IFT颗粒的对接和移动特别需要一种保守的纤毛蛋白DYF-1，因为OSM-3动蛋白是不活跃的，而在dyf-1突变体中，完整的IFT颗粒仅由Kinesin-II移动。这些发现表明，BBS睫状体疾病蛋白和OSM-3激动素激活剂参与了两条构建功能性纤毛的IFT途径的形成。
Cilia have diverse roles in motility and sensory reception, and defects in cilia function contribute to ciliary diseases such as Bardet-Biedl syndrome (BBS). Intraflagellar transport (IFT) motors assemble and maintain cilia by transporting ciliary precursors, bound to protein complexes called IFT particles, from the base of the cilium to their site of incorporation at the distal tip(1-3). In Caenorhabditis elegans, this is accomplished by two IFT motors, kinesin-II and osmotic avoidance defective (OSM)-3 kinesin, which cooperate to form two sequential anterograde IFT pathways that build distinct parts of cilia(4-7). By observing the movement of fluorescent IFT motors and IFT particles along the cilia of numerous ciliary mutants, we identified three genes whose protein products mediate the functional coordination of these motors. The BBS proteins BBS-7 and BBS-8 are required to stabilize complexes of IFT particles containing both of the IFT motors, because IFT particles in bbs-7 and bbs-8 mutants break down into two subcomplexes, IFT-A and IFT-B, which are moved separately by kinesin-II and OSM-3 kinesin, respectively. A conserved ciliary protein, DYF-1, is specifically required for OSM-3 kinesin to dock onto and move IFT particles, because OSM-3 kinesin is inactive and intact IFT particles are moved by kinesin-II alone in dyf-1 mutants. These findings implicate BBS ciliary disease proteins and an OSM-3 kinesin activator in the formation of two IFT pathways that build functional cilia.