Ciliopathies, including nephronophthisis (NPHP), Meckel syndrome (MKS) and Joubert syndrome (JBTS), can be caused by mutations affecting components of the transition zone, a domain near the base of the cilium that controls the protein composition of its membrane. We defined the three-dimensional arrangement of key proteins in the transition zone using two-colour stochastic optical reconstruction microscopy (STORM). NPHP and MKS complex components form nested rings comprised of nine-fold doublets. JBTS-associated mutations in RPGRIP1L or TCTN2 displace certain transition-zone proteins. Diverse ciliary proteins accumulate at the transition zone in wild-type cells, suggesting that the transition zone is a waypoint for proteins entering and exiting the cilium. JBTS-associated mutations in RPGRIP1L disrupt SMO accumulation at the transition zone and the ciliary localization of SMO. We propose that the disruption of transition-zone architecture in JBTS leads to a failure of SMO to accumulate at the transition zone and cilium, disrupting developmental signalling in JBTS.

中文翻译：

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超分辨率显微镜显示，睫状过渡区结构的破坏会导致Joubert综合征。

脊髓灰质炎包括肾病（NPHP），梅克尔综合征（MKS）和Joubert综合征（JBTS），可能是由影响过渡区成分的突变引起的，过渡区是纤毛基部附近的区域，该区域控制着其膜的蛋白质组成。我们使用两种颜色的随机光学重建显微镜（STORM）定义了过渡区中关键蛋白的三维排列。NPHP和MKS复杂组件形成由九折对偶构成的嵌套环。RPGRIP1L或TCTN2中与JBTS相关的突变取代了某些过渡区蛋白。各种各样的纤毛蛋白聚集在野生型细胞的过渡区中，这表明过渡区是蛋白质进入和离开纤毛的通道。RPGRIP1L中与JBTS相关的突变破坏了SMO在过渡区的积累和SMO的睫状定位。我们提出，JBTS中过渡区体系结构的破坏会导致SMO无法在过渡区和纤毛上积累，从而破坏JBTS中的发育信号。