Reconstitution reveals motor activation for intraflagellar transport

The human body represents a striking example of ciliary diversification. Extending from the surface of most cells, cilia accomplish an astonishingly diverse set of tasks. Predictably, mutations in ciliary genes cause a wide range of human diseases such as male infertility or blindness. In C. elegans sensory cilia, this functional diversity appears to be traceable to the differential regulation of the kinesin-2-powered intraflagellar transport (IFT) machinery. Here, we reconstituted the first functional, multi-component IFT complex that is deployed in the sensory cilia of C. elegans. Our bottom-up approach revealed the molecular basis of specific motor recruitment to the IFT trains. We identified the key component that incorporates homodimeric kinesin-2 into its physiologically relevant context which in turn allosterically activates the motor for efficient transport. These results lay the groundwork for a molecular delineation of IFT regulation that eluded understanding since its ground-breaking discovery more than two decades ago.