IFT88 maintains sensory cilia function in Drosophila melanogaster
Authors: Sascha Werner 1; Pilar Okenve-Ramos 1; Sihem Zitouni 2; Philip Hehlert 3; Susana Mendonça 5; Anje Sporbert 4; Christian Spalthoff 3; Martin C. Göpfert 3; Swadhin C. Jana 1; Mónica Bettencourt-Dias 1
Affiliations: 1) Instituto Gulbenkian de Ciência, Oeiras, Portugal; 2) Institut de Génétique Humaine (IGH) UMR 9002 CNRS, Montpellier, France; 3) Department of Cellular Neurobiology, University of Göttingen, Germany; 4) Advanced Light Microscopy, Max Delbrück Centrum for Molecular Medicine Berlin in the Helmholtz Associatio, Berlin, Germany; 5) Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.
Keywords: m. mechanosensation; e. intracellular transport
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/NOMPB, the Drosophila melanogaster orthologue of IFT88, continues to move along fully formed sensory cilia. We further identify the Drosophila Guanylyl Cyclase 2d (DmGucy2d/CG34357) and the TRPV channel subunit -Inactive- as DmIFT88 cargoes. In particular, DmIFT88 binds and is important for the localisation of the intracellular part of DmGucy2d, which is evolutionarily conserved and mutated in several degenerative retina diseases. We find that acute knockdown of DmIFT88 and DmGucy2d in ciliated neurons of adult flies leads to defects in the maintenance of cilium function, impairing hearing, and gravitaxis behaviour.
Our results show that cilia function requires an active maintenance program and that DmIFT88, and two cargoes, are important for this process. In addition, our work suggests that this maintenance program may be deregulated in degenerative human diseases where Guanylyl Cyclases are mutated.