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Related Concept Videos

Enzyme-linked Receptors01:00

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Related Experiment Video

Updated: May 17, 2026

Investigation of Synaptic Tagging/Capture and Cross-capture using Acute Hippocampal Slices from Rodents
11:29

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TrkB phosphorylation by Cdk5 is required for activity-dependent structural plasticity and spatial memory.

Kwok-On Lai1, Alan S L Wong, Man-Chun Cheung

  • 1Division of Life Science, The Hong Kong University of Science and Technology, Hong Kong, China.

Nature Neuroscience
|October 16, 2012
PubMed
Summary

Cyclin-dependent kinase 5 (Cdk5) phosphorylates the TrkB receptor at serine 478, a modification essential for spatial memory and learning. This phosphorylation regulates structural plasticity, impacting synaptic function and memory formation.

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Last Updated: May 17, 2026

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Published on: March 9, 2012

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Cell Biology

Background:

  • Brain-derived neurotrophic factor (BDNF) and its receptor TrkB are vital for neuronal functions, including synaptic plasticity, learning, and memory.
  • TrkB undergoes tyrosine autophosphorylation and serine phosphorylation at S478 by cyclin-dependent kinase 5 (Cdk5) upon BDNF binding.

Purpose of the Study:

  • To investigate the in vivo function of TrkB serine phosphorylation at S478.
  • To elucidate the role of Cdk5-mediated TrkB phosphorylation in synaptic plasticity and memory.

Main Methods:

  • Generation of knock-in mice lacking TrkB S478 phosphorylation (Trkb(S478A/S478A)).
  • Assessment of spatial memory and hippocampal long-term potentiation (LTP) in mutant mice.
  • Analysis of TrkB interactions and downstream signaling pathways involved in dendritic spine remodeling.

Main Results:

  • Trkb(S478A/S478A) mice exhibited impaired spatial memory and compromised hippocampal LTP.
  • S478 phosphorylation of TrkB is critical for its interaction with the guanine nucleotide exchange factor TIAM1.
  • This interaction leads to Rac1 activation and S6 ribosomal protein phosphorylation during activity-dependent dendritic spine remodeling.

Conclusions:

  • Cdk5-mediated S478 phosphorylation of TrkB is crucial for activity-dependent structural plasticity.
  • This phosphorylation event plays a vital role in long-term potentiation (LTP) and spatial memory formation.
  • The findings highlight a novel regulatory mechanism for synaptic plasticity and cognitive function.