Discovery and characterization of a pressure sensation and transduction (PREST) mechanism in the presynaptic terminal in the CNS.

2023 Fiscal Year Annual Research Report

• Project/Area Number: 21K15203
• Research Institution: The University of Tokyo
• Principal Investigator: UCAR HASAN 東京大学, ニューロインテリジェンス国際研究機構, 特任助教 (50748423)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: presynaptic plasticity / PREST / mechanical transmission / SV mobility

Outline of Annual Research Achievements

I discovered a new mechanism of synaptic vesicle(SV) mobility upon mechanical stimulation of the bouton. 1)Pushing causes dispersion of the SVs in bouton 2) Pushing enhances exocytosis in high-frequency stimulation 3)Synapsin, an SV binding protein, is also dispersed upon pushing 4)A dominant negative synapsin prevents SV dispersion, the Pr-increase and SNARE assembly that normally occurs after pushing 5)Inhibition of ERK1/2 also prevents SV dispersion, the Pr-increase and SNARE assembly that normally occurs after pushing. In summary, mobilization of SVs could enhance SV replenishment (a functional connection between 1 and 2 is to be established). These effects could be mediated by ERK phosphorylation on synapsin proteins (a functional connection between 3 and 4 is to be established).