TrkB phosphorylation by Cdk5 is required for activity-dependent structural plasticity and spatial memory
Publication in refereed journal

香港中文大學研究人員

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摘要The neurotrophin brain-derived neurotrophic factor (BDNF) and its receptor TrkB participate in diverse neuronal functions, including activity-dependent synaptic plasticity that is crucial for learning and memory. On binding to BDNF, TrkB is not only autophosphorylated at tyrosine residues but also undergoes serine phosphorylation at S478 by the serine/threonine kinase cyclin-dependent kinase 5 (Cdk5). However, the in vivo function of this serine phosphorylation remains unknown. We generated knock-in mice lacking this serine phosphorylation (Trkb(S478A/S478A) mice) and found that the TrkB phosphorylation deficient mice displayed impaired spatial memory and compromised hippocampal long-term potentiation (LIP). S478 phosphorylation of TrkB regulates its interaction with the Rac1-specific guanine nucleotide exchange factor TIAM1, leading to activation of Rac1 and phosphorylation of S6 ribosomal protein during activity-dependent dendritic spine remodeling. These findings reveal the importance of Cdk5-mediated S478 phosphorylation of TrkB in activity-dependent structural plasticity, which is crucial for LIP and spatial memory formation.
著者Lai KO, Wong ASL, Cheung MC, Xu P, Liang ZY, Lok KC, Xie H, Palko ME, Yung WH, Tessarollo L, Cheung ZH, Ip NY
期刊名稱Nature Neuroscience
詳細描述To ORKTS: doi: 10.1038/nn.3237
出版年份2012
月份11
日期1
卷號15
期次11
出版社Nature Publishing Group
頁次1506 - 1515
國際標準期刊號1097-6256
電子國際標準期刊號1546-1726
語言英式英語
Web of Science 學科類別Neurosciences; NEUROSCIENCES; Neurosciences & Neurology

上次更新時間 2020-20-11 於 00:39