Motility and microtubule depolymerization mechanisms of the Kinesin-8 motor, KIF19A

The cells that line the airways and other passages in the body have hair-like structures called cilia on their surface. Maintaining the cilia at an appropriate length is key to allowing fluid to flow efficiently in these passages. A protein called tubulin forms scaffolds known as microtubules that give each cilium its shape and allow it to change length. Motor proteins are also found in cilia, and travel along the microtubules to transport substances. One of these microtubule-based motors, referred to as KIF19A, accumulates at the tip of cilia and controls their length. It does so by combining two actions: it moves along the microtubule to the tip of the cilium, and then removes tubulin molecules from the end. Microtubules are straight along their length and curved at the end, and it is thought that kinesin recognizes both of these shapes in order to carry out these roles. A single region of the KIF19A protein appears to be able to accomplish both roles, but the molecular changes that the protein undergoes to do so are not known. Wang et al. have now investigated these changes by determining the structure of the motor domain of KIF19A from mice using two experimental approaches: X-ray crystallography and cryo-electron microscopy. These structures showed that the specific structural features responsible for the protein's dual roles are indeed clustered on the side of the protein that binds to the microtubule. Wang et al. also identified the regions that make KIF19A flexible enough to fit this interface with both straight and curved microtubules. Next, Wang et al. found that other regions of KIF19A stop it detaching from the microtubule and allow it to stabilize the curved shape of microtubule ends; this stimulates the microtubule to disassemble, or “depolymerize”. The findings show that KIF19A uses multiple strategies to enable it to carry out its roles. To understand better how KIF19A depolymerizes the microtubule, a more detailed structure of KIF19A together with tubulin will be needed. Structural studies of KIF19A in cilia will also be useful to understand how the protein controls the length of microtubules.