Cell Biology Program, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA.
Nat Cell Biol. 2013 Jun;15(6):591-601. doi: 10.1038/ncb2739. Epub 2013 May 5.
The transition zone is a specialized compartment found at the base of cilia, adjacent to the centriole distal end, where axonemal microtubules are heavily crosslinked to the surrounding membrane to form a barrier that gates the ciliary compartment. A number of ciliopathy molecules have been found to associate with the transition zone, but factors that directly recognize axonemal microtubules to specify transition zone assembly at the cilia base remain unclear. Here, through quantitative centrosome proteomics, we identify an axoneme-associated protein, CEP162 (KIAA1009), tethered specifically at centriole distal ends to promote transition zone assembly. CEP162 interacts with core transition zone components, and mediates their association with microtubules. Loss of CEP162 arrests ciliogenesis at the stage of transition zone assembly. Abolishing its centriolar tethering, however, allows CEP162 to stay on the growing end of the axoneme and ectopically assemble transition zone components at cilia tips. This generates extra-long cilia with strikingly swollen tips that actively release ciliary contents into the extracellular environment. CEP162 is thus an axoneme-recognition protein pre-tethered at centriole distal ends before ciliogenesis to promote and restrict transition zone formation specifically at the cilia base.
过渡区是纤毛底部的一个特化隔室，紧邻中心粒末端，此处轴丝微管与周围膜紧密交联，形成一个屏障，限制纤毛隔室的物质进出。已经发现许多纤毛病相关分子与过渡区相关联，但直接识别轴丝微管以在纤毛基部特异性组装过渡区的因素仍不清楚。在这里，通过定量中心体蛋白质组学，我们鉴定出一种轴丝相关蛋白 CEP162（KIAA1009），它特异性地固定在中心粒末端，以促进过渡区的组装。CEP162 与核心过渡区成分相互作用，并介导它们与微管的结合。CEP162 的缺失会使纤毛发生停滞在过渡区组装阶段。然而，消除其中心粒的束缚，CEP162 可以停留在轴丝的生长端，并在纤毛尖端异位组装过渡区成分。这会产生超长的纤毛，其尖端明显肿胀，并将纤毛内容物主动释放到细胞外环境中。因此，CEP162 是一种轴丝识别蛋白，在纤毛发生之前预先固定在中心粒末端，以促进和限制纤毛基部的过渡区形成。
