Myosin Va‑dependent Transport of NMDA Receptors in Hippocampal Neurons  

作　　者：Ru Gong Linwei Qin Linlin Chen Ning Wang Yifei Bao Wei Lu 

机构地区：[1]Ministry of Education(MOE)Key Laboratory of Developmental Genes and Human Disease,School of Life Science and Technology,Southeast University,Nanjing 210096,China [2]Department of Neurosurgery,State Key Laboratory of Medical Neurobiology,MOE Frontiers Center for Brain Science,Huashan Hospital,Institute for Translational Brain Research,Fudan University,Shanghai 200032,China [3]Department of Neurobiology,Nanjing Medical University,Nanjing 210096,China [4]Co‑innovation Center of Neuroregeneration,Nantong University,Nantong 226001,China

出　　处：《Neuroscience Bulletin》2024年第8期1053-1075,共23页神经科学通报（英文版）

基　　金：supported by grants from the STI2030-Major Projects(2021ZD0203502);the National Natural Science Foundation of China(31730107,31970959,and 31671056).

摘　　要：N-methyl-D-aspartate receptor(NMDAR)trafficking is a key process in the regulation of synaptic efficacy and brain function.However,the molecular mechanism underlying the surface transport of NMDARs is largely unknown.Here we identified myosin Va(MyoVa)as the specific motor protein that traffics NMDARs in hippocampal neurons.We found that MyoVa associates with NMDARs through its cargo binding domain.This association was increased during NMDAR surface transport.Knockdown of MyoVa suppressed NMDAR transport.We further demonstrated that Ca^(2+)/calmodulin-dependent protein kinase Ⅱ(CaMKⅡ)regulates NMDAR transport through its direct interaction with MyoVa.Furthermore,MyoVa employed Rab11 family-interacting protein 3(Rab11/FIP3)as the adaptor proteins to couple themselves with NMDARs during their transport.Accordingly,the knockdown of FIP3 impairs hippocampal memory.Together,we conclude that in hippocampal neurons,MyoVa conducts active transport of NMDARs in a CaMKII-dependent manner.

关 键 词：Myosin Va NMDA receptor CaMKⅡ TRANSPORT MEMORY 

分 类 号：R741[医药卫生—神经病学与精神病学]