Retracing the evolution of kinesin-2 deployment from mouse to worm

Abstract

SummaryDuring the course of evolution, cells have repurposed homologous motor proteins for the transport of an astonishingly diverse set of intracellular cargo. One prominent example of such diversification is the deployment of the respective kinesin-2 homologs in C. elegans (CeOSM-3) and mouse (MmKIF-17). While CeOSM-3 is deployed exclusively inside the cilium as a transport motor, its mouse counterpart behaves as a ciliary cargo. Instead, MmKIF-17 powers many different transport processes in the cytoplasm. Here we turned to functional reconstitution assays to uncover the molecular underpinnings of kinesin-2 deployment. Based on our findings, we propose that cells specified adaptor proteins as strictly conserved ‘on- and off-switches’, and ‘tailored’ the motors to fit the respective switches. This is exemplified by the surprising ability of the mouse adaptor to function as a ciliary on-switch for the distantly related CeOSM-3, but not for its own MmKIF-17 motor. Worms, in contrast, retained ciliary on- and off-switches, and can thus deploy CeOSM-3 as a regulatable transport motor inside the cilium. MmKIF-17 escaped this regulatory control by losing its interaction with the ciliary on-switch and has evidently been tailored to fit many different cytoplasmic adaptors over the course of evolution. We could further trace the robustness of an adaptor to serve as a conserved on-switch back to a few strictly conserved residues, which are also present in unicellular organisms. It is therefore conceivable that eukaryotes started to engineer dedicated on- and off-switches early in the evolution and kept their function conserved up to mammals.