Contribution of intraflagellar transport to compartmentalizationand maintenance of the photoreceptor cell

The first steps of vision take place in the ciliary outer segment compartment of photo-receptor cells. The protein composition of outer segments is uniquely suited to performthis function. The most abundant among these proteins is the visual pigment, rhodop-sin, whose outer segment trafficking involves intraflagellar transport (IFT). Here, wereport three major findings from the analysis of mice in which ciliary transport wasacutely impaired by conditional knockouts of IFT-B subunits. First, we demonstratethe existence of a sorting mechanism whereby mislocalized rhodopsin is recruited to andconcentrated in extracellular vesicles prior to their release, presumably to protect the cellfrom adverse effects of protein mislocalization. Second, reducing rhodopsin expressionsignificantly delays photoreceptor degeneration caused by IFT disruption, suggestingthat controlling rhodopsin levels may be an effective therapy for some cases of retinaldegenerative disease. Last, the loss of IFT-B subunits does not recapitulate a phenotypeobserved in mutants of the BBSome (another ciliary transport protein complex relyingon IFT) in which non-ciliary proteins accumulate in the outer segment. Whereas it iswidely thought that the role of the BBSome is to primarily participate in ciliary trans-port, our data suggest that the BBSome has another major function independent of IFTand possibly related to maintaining the diffusion barrier of the ciliary transition zone