Institute for Animal Developmental and Molecular Biology, Heinrich Heine University, 40225 Düsseldorf, Germany.
Sorbonne Université, CNRS UMR7622, INSERM U1156, Institut de Biologie Paris Seine (IBPS) - Developmental Biology Unit, 75005 Paris, France.
Mol Biol Cell. 2021 Apr 15;32(8):675-689. doi: 10.1091/mbc.E20-03-0190. Epub 2021 Feb 24.
A range of severe human diseases called ciliopathies is 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 localize 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 as it rescues ciliary gating in the absence of Rpgrip1l.
一系列被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。基体是从其中形成轴丝，即微管基的纤毛支架的修饰母中心粒。在轴丝的近端，过渡区作为控制纤毛蛋白进出的纤毛门。由于纤毛病通常是由于编码定位于 TZ 的蛋白质的基因突变引起的，因此了解 TZ 功能的机制非常重要。在这里，我们表明纤毛病蛋白 Rpgrip1l 通过确保脊椎动物 TZ 中 Cep290 的适当数量来控制纤毛门控。此外，我们发现类黄酮 eupatilin 可能是一种潜在的治疗方法，因为它可以在没有 Rpgrip1l 的情况下挽救纤毛门控。
