Myristoylation-dependent palmitoylation of cyclin Y modulates long-term potentiation and spatial learning

Jiyeon Seo, Hongik Hwang, Yuri Choi, Sunmin Jung, Jung Hwa Hong, Bong June Yoon, Hyewhon Rhim, Mikyoung Park

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

Abstract

Many psychiatric disorders accompany deficits in cognitive functions and synaptic plasticity, and abnormal lipid modifications of neuronal proteins are associated with their pathophysiology. Lipid modifications, including palmitoylation and myristoylation, play crucial roles in the subcellular localization and trafficking of proteins. Cyclin Y (CCNY), enriched in the postsynaptic compartment, acts as an inhibitory modulator of functional and structural long-term potentiation (LTP) in the hippocampal neurons. However, cellular and molecular mechanisms underlying CCNY-mediated inhibitory functions in the synapse remain largely unknown. Here, we report that myristoylation located CCNY to the trans-Golgi network (TGN), and subsequent palmitoylation directed the myristoylated CCNY from the TGN to the synaptic cell surface. This myristoylation-dependent palmitoylation of CCNY was required for the inhibitory role of CCNY in excitatory synaptic transmission, activity-induced dynamics of AMPA receptors and PSD-95, LTP, and spatial learning. Furthermore, spatial learning significantly reduced palmitoyl- and myristoyl-CCNY levels, indicating that spatial learning lowers the synaptic abundance of CCNY. Our findings provide mechanistic insight into how CCNY is clustered adjacent to postsynaptic sites where it could play its inhibitory roles in synaptic plasticity and spatial learning.

Original languageEnglish
Article number102349
JournalProgress in Neurobiology
Volume218
DOIs
Publication statusPublished - 2022 Nov

Bibliographical note

Funding Information:
We thank H. Kim, S. Kim, S. Kim, and J. Shim for their excellent technical support in providing primary neuronal cultures, and S. Kim for sampling mouse brains. HA-DHHC2 was a gift from M. Fukata (NIPS, Japan). This work was supported by grants received from the National Research Foundation of Korea (NRF) funded by the Korean government (MSIT) ( NRF-2018M3C7A1021848 , NRF-2021R1A2C2004606 , and NRF-2020R1A6A3A01095943 ) and by the Korea Institute of Science and Technology Institutional Program ( 2E31512 ).

Publisher Copyright:
© 2022 The Authors

Keywords

  • Cyclin Y
  • Long-term potentiation
  • Myristoylation
  • Palmitoylation
  • Spatial learning

ASJC Scopus subject areas

  • General Neuroscience

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