Comparative analysis of two Caenorhabditis elegans kinesins KLP-6 and UNC-104 reveals a common and distinct activation mechanism in kinesin-3

Abstract

Kinesin-3 is a family of microtubule-dependent motor proteins that transport various cargos within the cell. However, the mechanism underlying kinesin-3 activations remains elusive. In this study, we compared the biochemical properties of two Caenorhabditis elegans kinesin-3 family proteins, KLP-6 and UNC-104. Both KLP-6 and UNC-104 were predominantly monomeric in solution. As previously shown for UNC-104, non-processive KLP-6 monomer was converted to a processive motor when artificially dimerized. While it has long been thought that UNC-104 monomers do not have enough affinity to form homodimers, we found releasing the autoinhibition was sufficient to trigger dimerization of UNC-104 at nanomolar concentrations. In contrast, KLP-6 remained to be a non-processive monomer even when its autoinhibition was unlocked, suggesting a requirement of other factors for full activation. By examining the differences between KLP-6 and UNC-104, we identified a coiled-coil domain called CC2 that is required for the dimerization and processive movement of UNC-104. Our results suggest a common activation mechanism for kinesin-3 family members, while also highlighting their diversification.