Rules of the road: how to turn off kinesin motors

Intracellular organization is crucial for supporting cell function in an ever-changing environment. The eukaryotic microtubule cytoskeleton and its associated motor proteins are the vast molecular highways and motor vehicles that connect, position, and transport cellular cargoes, ranging from the cell nucleus to vesicles to mitotic spindles. The kinesin superfamily of motor proteins carries out a diverse array of functions and is thus a key player in these processes. While the mechanochemical cycle of kinesins has been extensively studied, mechanisms of kinesin activation and inhibition are not well understood. Over the past five years, several publications have significantly advanced our understanding of kinesin regulation, showing how inesin motors are turned off via autoinhibition and kinesin-binding protein. In this review, we will delve into these recent findings to introduce some 'rules of the road' in a model that captures the complexities of kinesin regulation.