TrkB phosphorylation by Cdk5 is required for activity-dependent structural plasticity and spatial memory
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AbstractThe 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.
All Author(s) ListLai KO, Wong ASL, Cheung MC, Xu P, Liang ZY, Lok KC, Xie H, Palko ME, Yung WH, Tessarollo L, Cheung ZH, Ip NY
Journal nameNature Neuroscience
Detailed descriptionTo ORKTS: doi: 10.1038/nn.3237
Volume Number15
Issue Number11
PublisherNature Publishing Group
Pages1506 - 1515
LanguagesEnglish-United Kingdom
Web of Science Subject CategoriesNeurosciences; NEUROSCIENCES; Neurosciences & Neurology

Last updated on 2020-20-10 at 01:02