The kinesin Kif21b regulates radial migration of cortical projection neurons through a non-canonical function on actin cytoskeleton

The kinesin Kif21b regulates radial migration of cortical projection neurons through a non-canonical function on actin cytoskeleton

The majority of the mechanisms and signaling processes that control radial migration converge on the cytoskeleton, and mutations in cytoskeletal proteins like actin-binding proteins, tubulins, and motor proteins have been associated with neuronal migration disorders. For example, mutation variants of the microtubule-binding kinesin protein, Kif21b, result in brain malformation through dysregulated neuronal formation; furthermore, depletion of the protein in mouse models led to deficits in neurological function. Recently, the Godin group identified a novel function of Kif21b that was important for cortical projection neuron migration. The group utilized novel genetic mouse models to specifically deplete Kif21b in neuronal cells, and through live cell imaging of brain slices they observed dysregulated neuronal migration.  Unexpectedly the group determined that Kif21b’s effect on radial migration was not entirely dependent on its microtubule-dependent function, as full length KiF21b restored proper migration, while the motor domain null mutant still partially rescued proper migration. Kif21b co-immunoprecipitation studies using mouse cortices were performed to identify alternative binding partners, and several of the 41 targets were actin or actin-associated proteins. Importantly, in vitro binding studies were performed to show that Kif21b bound directly to actin and affected its polymerization.  Additional studies showed that depletion of Kif21b led to aberrant actin dynamics which severely disrupted the radial migration of projection neurons.  Cytoskeleton Inc’s purified actin protein (Cat. # AKL99) was essential for confirming the Kif21b interaction with actin.  Accurate radial migration of pyramidal projection neurons is essential for proper neocortex function, and this study uncovers critical information about key proteins that regulate cytoskeletal processes.