We see the world through cilia. The outer segments of rods and cones are highly specialized sensory cilia, and the entire photosensing machinery including opsin is located in the outer segment and must be transported through a narrow connecting cilium that separates the outer segment from the cell body. But what motors drive this transport? A kinesin-driven motility called intraflagellar transport (IFT) was first discovered in the motile flagella of the unicellular green alga Chlamydomonas. IFT was found to be driven by a heterotrimeric kinesin-II motor. IFT has also been observed in the olfactory cilia of the nematode Caenorhabditis elegans, and again a heterotrimeric kinesin-II is required to drive this motility. Given that flagella and cilia from such two diverse species rely on the same kinesin-II-driven IFT process for transport, is it possible that IFT might also be needed in the connecting cilium of retinal photoreceptor cells?To investigate the role of IFT specifically in photoreceptor cells, Marszalek and colleagues1xGenetic evidence for selective transport of opsin and arrestin by kinesin-II in mammalian photoreceptors. Marszalek, J.R. et al. Cell. 2000; 102: 175–187Abstract | Full Text | Full Text PDF | PubMedSee all References1 constructed mice in which the gene encoding KIF3A, one of the kinesin-II subunits, contained a pair of loxP site-specific recombination sequences that, when excised, caused a frameshift owing to removal of one exon, thus leading to a completely nonfunctional protein sharing only the first methionine with the original protein. The Cre recombinase protein was then specifically expressed in rod cells under control of a photoreceptor-specific promoter.Loss of KIF3A caused extensive cell death among photoreceptor cells, leading to loss of as many as 80% of all rod cells. Ultrastructural analysis revealed that protein and vesicles accumulated at the base of the connecting cilium, suggesting that there might be a defect in transport of this material into the outer segment. Immunogold electron microscopy revealed that opsin is found in these deposits, showing that loss of KIF3A leads to a defect in opsin transport through the connecting cilium.Because defects in opsin transport are implicated in retinal degeneration diseases, might the cell death be caused by the defect in opsin transport? One hint that this could be true came from the fact that opsin mislocalization was observed prior to any observable cell death. To confirm this, retinas from the KIF3A conditional knockout mice were stained by immunofluorescence to detect opsin accumulation and simultaneously stained using a TUNEL assay to visualize apoptosis. It was found that 90% of all apoptotic cells showed defects in opsin localization, but a large fraction of cells with opsin accumulation defects did not show any signs of apoptosis. This implies that opsin accumulation must precede apoptosis.These results show that IFT is crucial for photoreceptor cell maintenance and suggest that defects in this transport process might underlie a range of retinal degeneration diseases in humans.