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IFT88 transports Gucy2d, a guanylyl cyclase, to maintain sensory cilia function in Drosophila

Werner, S.; Zitouni, S.; Okenve-Ramos, P.; Mendonca, S.; Sporbert, A.; Spalthoff, C.; Gopfert, M. C.; Jana, S. C.; Bettencourt-Dias, M.

2020-12-15 cell biology
10.1101/2020.12.15.417840 bioRxiv
Show abstract

Cilia are involved in a plethora of motility and sensory-related functions. Ciliary defects cause several ciliopathies, some of which with late-onset, suggesting cilia are actively maintained. While much is known about cilia assembly, little is understood about the mechanisms of their maintenance. Given that intraflagellar transport (IFT) is essential for cilium assembly, we investigated the role of one of its main players, IFT88, in ciliary maintenance. We show that DmIFT88, the Drosophila melanogaster orthologue of IFT88, continues to move along fully formed sensory cilia, and that its acute knockdown in the ciliated neurons of the adult affects sensory behaviour. We further identify DmGucy2d, the Drosophila guanylyl cyclase 2d, as a DmIFT88 cargo, whose loss also leads to defects in sensory behaviour maintenance. DmIFT88 binds to the intracellular part of DmGucy2d, which is evolutionarily conserved and mutated in several degenerative retina diseases, taking the cyclase into the cilia. Our results offer a novel mechanism for the maintenance of sensory cilia function and its potential role in human diseases.

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