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