Cdk5 is involved in BDNF-stimulated dendritic growth in hippocampal neurons

Zelda H Cheung1, Wing Hong Chin, Yu Chen

  • 1Department of Biochemistry, Biotechnology Research Institute and Molecular Neuroscience Center, Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China.

Plos Biology
|March 8, 2007
PubMed

Insights

Cyclin-dependent kinase 5 (Cdk5) phosphorylates the TrkB receptor, a key player in neuronal development. This interaction is crucial for brain-derived neurotrophic factor (BDNF)-induced dendritic growth.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Cell Biology

Background:

  • Neurotrophins regulate neuronal survival and differentiation.
  • Trk receptors (receptor tyrosine kinases) mediate neurotrophin functions.
  • Cyclin-dependent kinase 5 (Cdk5) may modulate receptor tyrosine kinase (RTK) signaling.

Purpose of the Study:

  • Investigate if Cdk5 modulates Trk signaling.
  • Identify TrkB as a Cdk5 substrate.
  • Elucidate Cdk5's role in neurotrophin-mediated neuronal growth.

Main Methods:

  • Biochemical assays to identify Cdk5 substrate.
  • Site-directed mutagenesis of TrkB.
  • Primary hippocampal neuron culture.
  • Analysis of dendritic growth and Cdc42 activation.

Main Results:

  • TrkB identified as a Cdk5 substrate, phosphorylated at Ser478.
  • Cdk5 inhibition or TrkB S478A mutation abolished BDNF-induced dendritic growth.
  • Cdk5 is involved in BDNF-induced activation of Rho GTPase Cdc42.

Conclusions:

  • Cdk5 directly phosphorylates TrkB at Ser478.
  • Cdk5 plays a critical role in BDNF-mediated dendritic growth.
  • Cdk5 modulates BDNF signaling via Cdc42 activation, impacting neuronal architecture.

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