KIF2C regulates synaptic plasticity and cognition in mice through dynamic microtubule depolymerization.
KIF2C regulates synaptic plasticity and cognition in mice through dynamic microtubule depolymerization.
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作者：
Zheng R;Du Y;Wang X;Liao T;Zhang Z;Wang N;Li X;Shen Y;Shi L;Luo J;Xia J;Wang Z;Xu J
动态微管在细胞结构和功能中起着至关重要的作用。在神经系统中，微管是货物蛋白运输的主要途径，它们专门延伸进出突触，调节突触的发育和可塑性。然而，调控突触和树突中动态微管的详细解聚机制尚不清楚。在本研究中，我们发现KIF2C是一种在神经系统中没有已知功能的动态微管解聚蛋白，在小鼠突触的结构和功能可塑性中起关键作用，并调节认知功能。通过其微管解聚能力，KIF2C调节树突中的微管动力学，并以神经元活动依赖的方式调节神经元中微管对棘的侵袭。通过RNAi敲除和条件敲除方法，我们发现KIF2C调节脊柱形态和AMPA受体的突触膜表达。此外，KIF2C缺乏导致小鼠兴奋传递受损、长期增强和认知行为改变。总之，我们的研究探索了KIF2C在神经系统中的新功能，并为活动依赖性微管动态如何调节突触可塑性和认知行为提供了重要的调节机制。
Dynamic microtubules play a critical role in cell structure and function. In nervous system, microtubules are the major route for cargo protein trafficking and they specially extend into and out of synapses to regulate synaptic development and plasticity. However, the detailed depolymerization mechanism that regulates dynamic microtubules in synapses and dendrites is still unclear. In this study, we find that KIF2C, a dynamic microtubule depolymerization protein without known function in the nervous system, plays a pivotal role in the structural and functional plasticity of synapses and regulates cognitive function in mice. Through its microtubule depolymerization capability, KIF2C regulates microtubule dynamics in dendrites, and regulates microtubule invasion of spines in neurons in a neuronal activity-dependent manner. Using RNAi knockdown and conditional knockout approaches, we showed that KIF2C regulates spine morphology and synaptic membrane expression of AMPA receptors. Moreover, KIF2C deficiency leads to impaired excitatory transmission, long-term potentiation, and altered cognitive behaviors in mice. Collectively, our study explores a novel function of KIF2C in the nervous system and provides an important regulatory mechanism on how activity-dependent microtubule dynamic regulates synaptic plasticity and cognition behaviors.