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Updated: May 11, 2026

Detection of Protein Palmitoylation in Cultured Hippocampal Neurons by Immunoprecipitation and Acyl-Biotin Exchange (ABE)
16:33

Detection of Protein Palmitoylation in Cultured Hippocampal Neurons by Immunoprecipitation and Acyl-Biotin Exchange (ABE)

Published on: February 18, 2013

Palmitoylation-dependent CDKL5-PSD-95 interaction regulates synaptic targeting of CDKL5 and dendritic spine

Yong-Chuan Zhu1, Dan Li, Lu Wang

  • 1Institute of Neuroscience and State Key Laboratory of Neuroscience, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.

Proceedings of the National Academy of Sciences of the United States of America
|May 15, 2013
PubMed

Insights

Cyclin-dependent kinase-like 5 (CDKL5) protein targets excitatory synapses via binding to postsynaptic density-95 (PSD-95). This interaction is crucial for normal dendritic spine development and is disrupted by pathogenic mutations in CDKL5 disorders.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Genetics

Background:

  • The X-linked gene cyclin-dependent kinase-like 5 (CDKL5) is implicated in severe neurodevelopmental disorders, including atypical Rett syndrome.
  • The precise function and regulation of CDKL5 protein within neurons are not fully understood.

Purpose of the Study:

  • To investigate the interaction between CDKL5 and postsynaptic density-95 (PSD-95).
  • To determine the role of this interaction in CDKL5 localization and neuronal development.
  • To explore the impact of pathogenic mutations on CDKL5-PSD-95 binding and synaptic function.

Main Methods:

  • Co-immunoprecipitation to assess CDKL5-PSD-95 binding.
  • Immunofluorescence microscopy to examine synaptic localization of CDKL5.
  • RNA interference (RNAi) to down-regulate CDKL5 expression.
  • Analysis of dendritic spine formation and growth.

Main Results:

  • CDKL5 directly binds to the scaffolding protein PSD-95, facilitating its targeting to excitatory synapses.
  • CDKL5-PSD-95 binding is regulated by palmitate cycling on PSD-95.
  • Pathogenic mutations truncating the C-terminal tail of CDKL5 reduce its binding to PSD-95 and synaptic accumulation.
  • Down-regulation of CDKL5 or disruption of the CDKL5-PSD-95 interaction impairs dendritic spine formation and growth.

Conclusions:

  • The palmitoylation-dependent interaction between CDKL5 and PSD-95 is critical for localizing CDKL5 to synapses, which is essential for normal spine development.
  • Disruption of this interaction by pathogenic CDKL5 mutations may contribute to the pathogenesis of CDKL5-related neurodevelopmental disorders.

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