1. Academic Validation
  2. Crosstalk of Synapsin1 palmitoylation and phosphorylation controls the dynamicity of synaptic vesicles in neurons

Crosstalk of Synapsin1 palmitoylation and phosphorylation controls the dynamicity of synaptic vesicles in neurons

  • Cell Death Dis. 2022 Sep 12;13(9):786. doi: 10.1038/s41419-022-05235-4.
Peipei Yan  # 1 2 Huicong Liu  # 1 2 Tao Zhou 2 Pu Sun 2 Yilin Wang 2 Xibin Wang 2 Lin Zhang 2 Tian Wang 2 Jing Dong 2 Jiangli Zhu 3 Luxian Lv 1 Wenqiang Li 1 Shiqian Qi 3 Yinming Liang 4 Eryan Kong 5 6
Affiliations

Affiliations

  • 1 The Second Affiliated Hospital of Xinxiang Medical University, Xinxiang, China.
  • 2 Institute of Psychiatry and Neuroscience, Xinxiang key laboratory of protein palmitoylation and major human diseases, Xinxiang Medical University, Xinxiang, China.
  • 3 Department of Urology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and National Collaborative Innovation Center, 610041, Chengdu, China.
  • 4 Laboratory of Genetic Regulators in the Immune System, Henan Key Laboratory of Immunology and Targeted Therapy, School of Laboratory Medicine, Xinxiang Medical University, Xinxiang, China.
  • 5 The Second Affiliated Hospital of Xinxiang Medical University, Xinxiang, China. [email protected].
  • 6 Institute of Psychiatry and Neuroscience, Xinxiang key laboratory of protein palmitoylation and major human diseases, Xinxiang Medical University, Xinxiang, China. [email protected].
  • # Contributed equally.
Abstract

The dynamics of synaptic vesicles (SVs) within presynaptic domains are tightly controlled by synapsin1 phosphorylation; however, the mechanism underlying the anchoring of synapsin1 with F-actin or SVs is not yet fully understood. Here, we found that Syn1 is modified with protein palmitoylation, and examining the roles of Syn1 palmitoylation in neurons led us to uncover that Syn1 palmitoylation is negatively regulated by its phosphorylation; together, they manipulate the clustering and redistribution of SVs. Using the combined approaches of electron microscopy and genetics, we revealed that Syn1 palmitoylation is vital for its binding with F-actin but not SVs. Inhibition of Syn1 palmitoylation causes defects in SVs clustering and a reduced number of total SVs in vivo. We propose a model in which SVs redistribution is triggered by upregulated Syn1 phosphorylation and downregulated Syn1 palmitoylation, and they reversibly promote SVs clustering. The crosstalk of Syn1 palmitoylation and phosphorylation thereby bidirectionally manipulates SVs dynamics in neurons.

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