Abstract
Neurons require a well-coordinated intercellular transport system to maintain their normal cellular function and morphology. The kinesin family of proteins (KIFs) fills this role by regulating the transport of a diverse array of cargos in post-mitotic cells. On the other hand, in mitotic cells, KIFs facilitate the fidelity of the cellular division machinery. Though certain mitotic KIFs function in post-mitotic neurons, little is known about them. We studied the role of a mitotic KIF (KIF3B) in neuronal architecture. We find that the RNAi mediated knockdown of KIF3B in primary cortical neurons resulted in an increase in spine density; the number of thin and mushroom spines; and dendritic branching. Consistent with the change in spine density, we observed a specific increase in the distribution of the excitatory post-synaptic protein, PSD-95 in KIF3B knockdown neurons. Interestingly, overexpression of KIF3B produced a reduction in spine density, in particular mushroom spines, and a decrease in dendritic branching. These studies suggest that KIF3B is a key determinant of cortical neuron morphology and that it functions as an inhibitory constraint on structural plasticity, further illuminating the significance of mitotic KIFs in post-mitotic neurons.