PKD1 promotes functional synapse formation coordinated with N-cadherin in hippocampus

Cheng Cen, Li Da Luo, Wen Qi Li, Gang Li, Na Xi Tian, Ge Zheng, Dong Min Yin, Yimin Zou, Yun Wang

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Functional synapse formation is critical for the wiring of neural circuits in the developing brain. The cell adhesion molecule N-cadherin plays important roles in target recognition and synaptogenesis. However, the molecular mechanisms that regulate the localization of N-cadherin and the subsequent effects remain poorly understood. Here, we show that protein kinase D1 (PKD1) directly binds to N-cadherin at amino acid residues 836–871 and phosphorylates it at Ser 869, 871, and 872, thereby increasing the surface localization of N-cadherin and promoting functional synapse formation in primary cultured hippocampal neurons obtained from embryonic day 18 rat embryos of either sex. Intriguingly, neuronal activity enhances the interactions between N-cadherin and PKD1, which are critical for the activity-dependent growth of dendritic spines. Accordingly, either disruption the binding between N-cadherin and PKD1 or preventing the phosphorylation of N-cadherin by PKD1 in the hippocampal CA1 region of male rat leads to the reduction in synapse number and impairment of LTP. Together, this study demonstrates a novel mechanism of PKD1 regulating the surface localization of N-cadherin and suggests that the PKD1-N-cadherin interaction is critical for synapse formation and function.

Original languageEnglish (US)
Pages (from-to)183-199
Number of pages17
JournalJournal of Neuroscience
Volume38
Issue number1
DOIs
StatePublished - Jan 3 2018

Keywords

  • Activity-dependent
  • N-cadherin
  • Protein kinase D1
  • Synapse formation
  • Synaptic plasticity

ASJC Scopus subject areas

  • Neuroscience(all)

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  • Cite this

    Cen, C., Luo, L. D., Li, W. Q., Li, G., Tian, N. X., Zheng, G., Yin, D. M., Zou, Y., & Wang, Y. (2018). PKD1 promotes functional synapse formation coordinated with N-cadherin in hippocampus. Journal of Neuroscience, 38(1), 183-199. https://doi.org/10.1523/JNEUROSCI.1640-17.2017