Ciliopathies affect a variety of tissues during development including the heart, kidneys, respiratory tract, and retina. Though an increasing number of monogenic causes of ciliopathies have been described, many remain unexplained. Recently, recessive variants in NUP93 and NUP205 encoding two proteins of the inner ring of the nuclear pore complex were implicated as causes of steroid resistant nephrotic syndrome. In addition, we previously found that the inner ring nucleoporins NUP93 and NUP188 function in proper left-right patterning in developing embryos via a role at the cilium. Here, we describe the role of an additional inner ring nucleoporin NUP205 in cilia biology and establishment of normal organ situs. Using knockdown in Xenopus, we show that Nup205 depletion results in loss of cilia and abnormal cardiac morphology. Furthermore, by transmission electron microscopy, we observe a loss of cilia and mispositioning of intracellular ciliary structures such as basal bodies and rootlets upon depleting inner ring nucleoporins. We describe a model wherein NUP93 interacting with either NUP188 or NUP205 is necessary for cilia. We thus provide evidence that dysregulation of inner ring nucleoporin genes that have been identified in patients may contribute to pathogenesis through cilia dysfunction.

纤毛病在发育过程中会影响多种组织，包括心脏、肾脏、呼吸道和视网膜。尽管已经描述了越来越多的纤毛病单基因原因，但仍有许多原因无法解释。最近，NUP93和NUP205 中编码核孔复合物内环的两种蛋白质的隐性变异被认为是类固醇抵抗性肾病综合征的原因。此外，我们之前发现内环核孔蛋白 NUP93 和 NUP188 通过在纤毛上的作用在发育胚胎的适当左右模式中起作用。在这里，我们描述了额外的内环核孔蛋白 NUP205 在纤毛生物学和正常器官位置建立中的作用。在非洲爪蟾中使用击倒，我们表明 Nup205 耗竭导致纤毛丧失和心脏形态异常。此外，通过透射电子显微镜，我们观察到纤毛丢失和细胞内纤毛结构（如基体和小根）在消耗内环核孔蛋白时错位。我们描述了一个模型，其中 NUP93 与 NUP188 或 NUP205 相互作用是纤毛所必需的。因此，我们提供的证据表明，已在患者中发现的内环核孔蛋白基因的失调可能通过纤毛功能障碍导致发病。