A ciliopathy complex at the transition zone protects the cilia as a privileged membrane domain
A ciliopathy complex at the transition zone protects the cilia as a privileged membrane domain
复制标题
DOI：
10.1038/ncb2410
复制
发表时间：
2012-01-01
影响因子：
21.3
通讯作者：
Peterson, Andrew S.
中科院分区：
文献类型：
--
作者：
Chih, Ben;Liu, Peter;Peterson, Andrew S.
使用RNAi筛选，蛋白质组学，细胞生物学和小鼠遗传学方法，我们已经确定了9种蛋白质的复合物，其中7种在人类纤毛病中被破坏。一个跨膜组件，TMEM231，定位到基体之前，独立于鞭毛内运输的隔蛋白2（Sept2）调节的方式。TMEM 231、B9 D1（含B9结构域的蛋白1）和CC2D2A（含卷曲螺旋和C2结构域的蛋白2A）在过渡区的定位相互依赖，并依赖于Sept2。在体外破坏复合物会导致纤毛形成减少和剩余纤毛的信号受体丢失。敲除B9D1和TMEM 231的小鼠在Sonic hedgehog（Shh）信号传导和纤毛发生中具有相同的缺陷。引人注目的是，复合物的破坏增加了向纤毛膜的扩散速率和纤毛中质膜蛋白的量。我们所描述的复合物对于正常纤毛功能是必不可少的，并且作为扩散屏障来维持纤毛膜作为区室化的信号细胞器。
Using RNAi screening, proteomics, cell biological and mouse genetics approaches, we have identified a complex of nine proteins, seven of which are disrupted in human ciliopathies. A transmembrane component, TMEM231, localizes to the basal body before and independently of intraflagellar transport in a Septin 2 (Sept2)-regulated fashion. The localizations of TMEM231, B9D1 (B9 domain-containing protein 1) and CC2D2A (coiled-coil and C2 domain-containing protein 2A) at the transition zone are dependent on one another and on Sept2. Disruption of the complex in vitro causes a reduction in cilia formation and a loss of signalling receptors from the remaining cilia. Mouse knockouts of B9D1 and TMEM231 have identical defects in Sonic hedgehog (Shh) signalling and ciliogenesis. Strikingly, disruption of the complex increases the rate of diffusion into the ciliary membrane and the amount of plasma-membrane protein in the cilia. The complex that we have described is essential for normal cilia function and acts as a diffusion barrier to maintain the cilia membrane as a compartmentalized signalling organelle.