Microtubule binding of the kinesin-4 KIF7 and its regulation by autoinhibition

Abstract

KIF7 is a member of the kinesin-4 family and plays critical roles in Hedgehog signaling in vertebrate cells. KIF7 is an atypical kinesin as it binds to microtubules but is immotile. We demonstrate that, like conventional kinesins, KIF7 is regulated by autoinhibition as the full-length motor cannot bind to microtubules whereas truncated versions bind statically to microtubules in cells. Previous work suggested that truncated KIF7 motors bind preferentially to the plus ends of microtubules in vitro, however, we find that truncated KIF7 does not bind preferentially to or track the plus ends of growing microtubules in mammalian cells or in cell extracts. Although the truncated KIF7 did alter microtubule dynamics in cells, this property is not specific to KIF7 as expression of an active kinesin-1 motor also altered microtubule growth rates. The immotile behavior of KIF7 is not due to the extended neck linker domain as its deletion does not activate KIF7 for motility and its presence in a KIF5C/KIF7 chimeric motor does not prevent processive motility. Together this work indicates that the atypical kinesin KIF7 is regulated by autoinhibition to prevent binding to microtubules and alteration of microtubule dynamics in cells.