Joseph Nadine F, Grinman Eddie, Swarnkar Supriya, Puthanveettil Sathyanarayanan V
The Skaggs Graduate School of Chemical and Biological Sciences, The Scripps Research Institute, La Jolla, CA, United States.
Department of Neuroscience, The Scripps Research Institute, Jupiter, FL, United States.
Front Cell Neurosci. 2020 Oct 19;14:521199. doi: 10.3389/fncel.2020.521199. eCollection 2020.
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.
神经元需要一个协调良好的细胞间运输系统来维持其正常的细胞功能和形态。驱动蛋白家族蛋白（KIFs）通过调节有丝分裂后细胞中各种货物的运输来发挥这一作用。另一方面，在有丝分裂细胞中，KIFs促进细胞分裂机制的保真度。尽管某些有丝分裂KIFs在有丝分裂后神经元中发挥作用，但人们对它们知之甚少。我们研究了一种有丝分裂KIF（KIF3B）在神经元结构中的作用。我们发现，RNA干扰介导的原代皮质神经元中KIF3B的敲低导致棘突密度增加；细棘突和蘑菇状棘突的数量增加；以及树突分支增加。与棘突密度的变化一致，我们观察到在KIF3B敲低的神经元中，兴奋性突触后蛋白PSD-95的分布有特异性增加。有趣的是，KIF3B的过表达导致棘突密度降低，尤其是蘑菇状棘突，以及树突分支减少。这些研究表明，KIF3B是皮质神经元形态的关键决定因素，并且它作为对结构可塑性的抑制性限制发挥作用，进一步阐明了有丝分裂KIFs在有丝分裂后神经元中的重要性。
