Molecular Motor KIF3B Acts as a Key Regulator of Dendritic Architecture in Cortical Neurons

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.

Molecular motor KIF3B in the prelimbic cortex constrains the consolidation of contextual fear memory

“…To assess whether deficits in memory due to KIF3B depletion can be attributed to a structural change in prelimbic neurons, we next carried out dendritic imaging analysis in the prelimbic cortex. Previous studies have shown that KIF3B plays a role in the structural morphology of neurons [ 30 , 38 ], and work from our lab has found that KIF3B knockdown in cortical neurons causes an increase in dendritic arborization [ 30 ]. We have also found that KIF3B depletion increases the number of mushroom and thin spines [ 30 ].…”

“…Previous studies have shown that KIF3B plays a role in the structural morphology of neurons [ 30 , 38 ], and work from our lab has found that KIF3B knockdown in cortical neurons causes an increase in dendritic arborization [ 30 ]. We have also found that KIF3B depletion increases the number of mushroom and thin spines [ 30 ]. Alsabban et al found a similar increase in mushroom spines of dissociated hippocampal neurons from KIF3B mutant mice [ 38 ].…”

“…Our own lab demonstrated that KIF11 KD (knockdown) in hippocampal neurons increased dendritic branching without a change in spine density [ 29 ]. Similarly, it has been shown that knockdown of KIF3B in cortical neurons causes an increase in dendritic arborization, with an increase in mushroom and thin spines as well [ 30 ]. In contrast, KIF21B KD neurons have reduced dendritic branching [ 31 ], which also includes a reduction in mushroom and stubby spines.…”

Double Duty: Mitotic Kinesins and Their Post-Mitotic Functions in Neurons

“…KIF3B also has a dendritic phenotype. Post-developmental knockdown of KIF3B in dissociated cortical neurons showed that the overall density of dendritic spines was increased [ 56 ]. This corresponded with an increase in both mushroom and thin spines [ 56 ].…”

“…Post-developmental knockdown of KIF3B in dissociated cortical neurons showed that the overall density of dendritic spines was increased [ 56 ]. This corresponded with an increase in both mushroom and thin spines [ 56 ]. Dendritic branching and growth are mediated by microtubule polymerization [ 57 ].…”