Common general anesthetic propofol impairs kinesin processivity

Significance Kinesins are major transporters of cargos toward the cell periphery. They are highly expressed in the CNS, and their dysfunction leads to a wide range of human pathologies, including neurodevelopmental and neurodegenerative diseases, ciliopathies, epilepsy, and birth defects. We have discovered that the widely used general anesthetic propofol shortens the distance that kinesins travel, but their velocity remains unchanged. These results suggest that propofol is not binding at the ATP site or allosteric sites that affect ATP turnover, leading to the conclusion that the allosteric sites form on microtubule association. We postulate that general anesthetics bind specifically to transport kinesins and/or the kinesin–β-tubulin interface, and diminish their ability to transport critical cargos, thereby contributing to the pleiotropic state of anesthesia.