Myosin IIb-dependent Regulation of Actin Dynamics Is Required for N-Methyl-D-aspartate Receptor Trafficking during Synaptic Plasticity.
N-Methyl-d-aspartate receptor (NMDAR) synaptic incorporation changes the number of NMDARs at synapses and is thus critical to various NMDAR-dependent brain functions. To date, the molecules involved in NMDAR trafficking and the underlying mechanisms are poorly understood. Here, we report that myosin IIb is an essential molecule in NMDAR synaptic incorporation during PKC- or θ burst stimulation-induced synaptic plasticity. Moreover, we demonstrate that myosin light chain kinase (MLCK)-dependent actin reorganization contributes to NMDAR trafficking. The findings from additional mutual occlusion experiments demonstrate that PKC and MLCK share a common signaling pathway in NMDAR-mediated synaptic regulation. Because myosin IIb is the primary substrate of MLCK and can regulate actin dynamics during synaptic plasticity, we propose that the MLCK- and myosin IIb-dependent regulation of actin dynamics is required for NMDAR trafficking during synaptic plasticity. This study provides important insights into a mechanical framework for understanding NMDAR trafficking associated with synaptic plasticity.
From the Department of Neurobiology, Nanjing Medical University, Nanjing, Jiangsu Province 210029, China.
Yunfei
Y
Bu
From the Department of Neurobiology, Nanjing Medical University, Nanjing, Jiangsu Province 210029, China, the Key Laboratory of Developmental Genes and Human Disease of the Ministry of Education of China, Institute of Life Sciences, Southeast University, Nanjing, Jiangsu Province 210096, China.
Ning
N
Wang
From the Department of Neurobiology, Nanjing Medical University, Nanjing, Jiangsu Province 210029, China, the Key Laboratory of Developmental Genes and Human Disease of the Ministry of Education of China, Institute of Life Sciences, Southeast University, Nanjing, Jiangsu Province 210096, China.
Shaoli
S
Wang
From the Department of Neurobiology, Nanjing Medical University, Nanjing, Jiangsu Province 210029, China, the Key Laboratory of Developmental Genes and Human Disease of the Ministry of Education of China, Institute of Life Sciences, Southeast University, Nanjing, Jiangsu Province 210096, China.
Tao
T
Sheng
From the Department of Neurobiology, Nanjing Medical University, Nanjing, Jiangsu Province 210029, China.
Tian
T
Tian
From the Department of Neurobiology, Nanjing Medical University, Nanjing, Jiangsu Province 210029, China.
Linlin
L
Chen
From the Department of Neurobiology, Nanjing Medical University, Nanjing, Jiangsu Province 210029, China.
Weiwei
W
Pan
the Key Laboratory of Model Animal for Disease Study of the Ministry of Education of China, Model Animal Research Center, Nanjing University, Nanjing, Jiangsu Province 210063, China, and.
Minsheng
M
Zhu
the Department of Neurobiology, Key Laboratory of Medical Neurobiology of the Ministry of Health of China, Zhejiang Province Key Laboratory of Neurobiology, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province 310058, China.
Jianhong
J
Luo
From the Department of Neurobiology, Nanjing Medical University, Nanjing, Jiangsu Province 210029, China, the Key Laboratory of Developmental Genes and Human Disease of the Ministry of Education of China, Institute of Life Sciences, Southeast University, Nanjing, Jiangsu Province 210096, China, the Co-innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu Province 226001, China, luwei@seu.edu.cn.
Wei
W
Lu
D000199:Actins / Q000502:physiology*; D000818:Animals; D004789:Enzyme Activation; D006624:Hippocampus / Q000502:physiology; D066298:In Vitro Techniques; D051379:Mice; D018345:Mice, Knockout; D009219:Myosin-Light-Chain Kinase / Q000235:genetics / Q000378:metabolism; D009473:Neuronal Plasticity; D024501:Nonmuscle Myosin Type IIB / Q000502:physiology*; D011493:Protein Kinase C / Q000378:metabolism; D021381:Protein Transport; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*
D000199:Actins; D016194:Receptors, N-Methyl-D-Aspartate; D011493:Protein Kinase C; D009219:Myosin-Light-Chain Kinase; D024501:Nonmuscle Myosin Type IIB
NMDA receptor; actin; myosin; myosin IIb; patch clamp; protein kinase C (PKC); synaptic plasticity; trafficking