Department of Cellular Biology, University of Georgia, Athens, GA.
Laboratory of Cytoskeleton and Cilia Biology, Nencki Institute of Experimental Biology of Polish Academy of Sciences, Warsaw, Poland.
J Cell Biol. 2018 Dec 3;217(12):4298-4313. doi: 10.1083/jcb.201804141. Epub 2018 Sep 14.
Cilia, essential motile and sensory organelles, have several compartments: the basal body, transition zone, and the middle and distal axoneme segments. The distal segment accommodates key functions, including cilium assembly and sensory activities. While the middle segment contains doublet microtubules (incomplete B-tubules fused to complete A-tubules), the distal segment contains only A-tubule extensions, and its existence requires coordination of microtubule length at the nanometer scale. We show that three conserved proteins, two of which are mutated in the ciliopathy Joubert syndrome, determine the geometry of the distal segment, by controlling the positions of specific microtubule ends. FAP256/CEP104 promotes A-tubule elongation. CHE-12/Crescerin and ARMC9 act as positive and negative regulators of B-tubule length, respectively. We show that defects in the distal segment dimensions are associated with motile and sensory deficiencies of cilia. Our observations suggest that abnormalities in distal segment organization cause a subset of Joubert syndrome cases.
纤毛是重要的运动和感觉细胞器，具有几个隔室：基体、过渡区以及中间和远端轴丝段。远端段容纳关键功能，包括纤毛组装和感觉活动。虽然中间段包含双联微管（与完整 A 微管融合的不完整 B 微管），但远端段仅包含 A 微管延伸，其存在需要纳米尺度上微管长度的协调。我们表明，三个保守蛋白（其中两个在纤毛病杰氏综合征中发生突变）通过控制特定微管末端的位置来确定远端段的几何形状。FAP256/CEP104 促进 A 微管伸长。 CHE-12/Crescerin 和 ARMC9 分别作为 B 微管长度的正调节剂和负调节剂。我们表明，远端段尺寸的缺陷与纤毛的运动和感觉缺陷有关。我们的观察表明，远端段组织的异常导致了杰氏综合征病例的一部分。
