A range of severe human diseases called ciliopathies are caused by the dysfunction of primary cilia. Primary cilia are cytoplasmic protrusions consisting of the basal body (BB), the axoneme and the transition zone (TZ). The BB is a modified mother centriole from which the axoneme, the microtubule-based ciliary scaffold, is formed. At the proximal end of the axoneme, the TZ functions as the ciliary gate governing ciliary protein entry and exit. Since ciliopathies often develop due to mutations in genes encoding proteins that localise to the TZ, the understanding of the mechanisms underlying TZ function is of eminent importance. Here, we show that the ciliopathy protein Rpgrip1l governs ciliary gating by ensuring the proper amount of Cep290 at the vertebrate TZ. Further, we identified the flavonoid eupatilin as a potential agent to tackle ciliopathies caused by mutations in RPGRIP1L as it rescues ciliary gating in the absence of Rpgrip1l.

一系列称为纤毛病的严重人类疾病是由初级纤毛功能障碍引起的。初级纤毛是由基体 (BB)、轴丝和过渡区 (TZ) 组成的细胞质突起。BB 是一种改良的母中心粒，从中形成轴丝，即基于微管的纤毛支架。在轴丝的近端，TZ 充当控制纤毛蛋白进出的纤毛门。由于纤毛病的发生通常是由于编码位于 TZ 的蛋白质的基因发生突变，因此了解 TZ 功能的潜在机制非常重要。在这里，我们展示了纤毛病蛋白 Rpgrip1l 通过确保脊椎动物 TZ 上适量的 Cep290 来控制纤毛门控。更远，RPGRIP1L因为它在没有 Rpgrip1l 的情况下拯救了纤毛门控。