Login / Signup

N-acetylation of α-synuclein enhances synaptic vesicle clustering mediated by α-synuclein and lysophosphatidylcholine.

Chuchu WangChunyu ZhaoXiao HuJiali QiangZhenying LiuJinge GuShengnan ZhangDan LiYaoyang ZhangJacqueline BurréJiajie DiaoCong Liu
Published in: bioRxiv : the preprint server for biology (2024)
Post-translational modifications (PTMs) of α-synuclein (α-syn) such as acetylation and phosphorylation play important yet distinct roles in regulating α-syn conformation, membrane binding, and amyloid aggregation. However, how PTMs regulate α-syn function in presynaptic terminals remains unclear. Previously, we reported that α-syn clusters synaptic vesicles (SV) 1 , and neutral phospholipid lysophosphatidylcholine (LPC) can mediate this clustering 2 . Here, based on our previous findings, we further demonstrate that N-terminal acetylation, which occurs under physiological condition and is irreversible in mammalian cells, significantly enhances the functional activity of α-syn in clustering SVs. Mechanistic studies reveal that this enhancement is caused by the N-acetylation-promoted insertion of α-syn's N-terminus and increased intermolecular interactions on the LPC-containing membrane. Our work demonstrates that N-acetylation fine-tunes α-syn-LPC interaction for mediating α-syn's function in SV clustering.
Keyphrases
  • single cell
  • histone deacetylase
  • rna seq
  • gene expression
  • fatty acid
  • molecular dynamics simulations
  • prefrontal cortex