Abstract
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.
Highlights
Microtubules (MTs) are eukaryotic cytoskeletons that play an important role in cell function
Previous studies have showed that KIF2C plays an important role during cell division in mitotic cells (Andrews et al, 2004; Lan et al, 2004; Sanhaji et al, 2014); it is not clear whether KIF2C is present in the nervous system
The results showed that KIF2C was expressed in a development-related pattern in cultured neurons: detectable at day in vitro 3 (DIV 3) and significantly increased at DIV 10
Summary
Microtubules (MTs) are eukaryotic cytoskeletons that play an important role in cell function. The MTs dynamic instability, that is the growing or shrinking of MT plus end, has been detected in both shaft and dendritic protrusions (Mitchison and Kirschner, 1984) and is involved in spine formation and synaptic function (Hu et al, 2008; Gu et al, 2008; Merriam et al, 2011; Tada and Sheng, 2006). MTs can be regulated to extend from the dendritic shaft into spines and affect synaptic structure and function (3-8), which could be an important event for synaptic plasticity. Regulatory mechanism underlying MT dynamics in or out from synapse upon neuronal activity is still unclear, nor its role in learning and memory
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
