Loss-of-function of the ciliopathy protein Cc2d2a disorganizes the vesicle fusion machinery at the periciliary membrane and indirectly affects Rab8-trafficking in zebrafish photoreceptors

• DOI: 10.1371/journal.pgen.1007150
• Publication Date: 2017-12-27T18:33:08Z
• Authors: Irene Ojeda Naharros; Matthias Gesemann; José M. Mateos; Gery Barmettler; Austin Forbes; Urs Ziegler; Stephan C. F. Neu...; Ruxandra Bachmann...
• Keywords: Opsin; Transport protein; Exocyst; SNAP25; Vesicular Transport Proteins; Vesicle fusion

Ciliopathies are human disorders caused by dysfunction of primary cilia, ubiquitous organelles involved in transduction environmental signals such as light sensation photoreceptors. Concentration signal detection proteins opsins the ciliary membrane is achieved RabGTPase-regulated polarized vesicle trafficking and a selective barrier at base, transition zone (TZ). Dysfunction TZ protein CC2D2A causes Joubert/Meckel syndromes humans loss localization animal models, including retinal The link between upstream has been little explored to date. Moreover, role small GTPase Rab8 opsin-carrier (OCV) recently questioned mouse model. Using correlative electron microscopy live imaging zebrafish photoreceptors, we provide first characterization Rab8-mediated photoreceptors vivo. Our results support possibly redundant for both Rab8a/b paralogs OCV trafficking, based on co-localization vesicular structures, joint movement Rab8-tagged particles with opsin. We further investigate Cc2d2a using cc2d2a mutants identify requirement latest step namely fusion. Progressive accumulation opsin-containing vesicles apical portion lacking disorganization fusion machinery periciliary mislocalization t-SNAREs SNAP25 Syntaxin3 exocyst component Exoc4. observe secondary defects Rab8-trafficking cytoplasmic Rab8. Taken together, our participation novel incoming ciliary-directed vesicles, through organization membrane.