Rpgrip1l controls ciliary gating by ensuring the proper amount of Cep290 at the vertebrate transition zone

Antonia Wiegering (1, 2) , Renate Dildrop (2) , Christine Vesque (3, 4) , Hemant Khanna (5) , Sylvie Schneider-Maunoury (3, 4) , Christoph Gerhardt (2)

1 LBD - Laboratoire de Biologie du Développement [IBPS]
2 Heinrich Heine Universität Düsseldorf = Heinrich Heine University [Düsseldorf]
3 LBD-E10 - Morphogénèse du Cerveau des Vertébrés = Morphogenesis of the vertebrate brain
4 IBPS - Institut de Biologie Paris Seine
5 UMASS - University of Massachusetts Medical School [Worcester]

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.

Domains: Life Sciences [q-bio]

Antonia Wiegering, Renate Dildrop, Christine Vesque, Hemant Khanna, Sylvie Schneider-Maunoury, et al.. Rpgrip1l controls ciliary gating by ensuring the proper amount of Cep290 at the vertebrate transition zone. Molecular Biology of the Cell, 2021, pp.mbc.E20-03-0190. ⟨10.1091/mbc.E20-03-0190⟩. ⟨hal-03152399⟩