This multidisciplinary work led by Marieke Meijer (Amsterdam UMC – FGA) describes how tomosyns limit synaptic strength at rest to equalize synaptic transmission during activity.
This study explains at the molecular level why synapses are stronger and depress faster in the absence of tomosyns. The research was mainly performed by Marieke Meijer (Amsterdam UMC), Miriam Öttl (Vrije Universiteit) and Jie Yang (Yale School of Medicine), among others, who combined synapse physiology on a conditional mouse model of tomosyn deficiency with single-molecule force measurements by the Yongli Zhang lab. Our data reveal that tomosyns produce a new intermediate state in SNARE assembly which drastically reduces the probability that synaptic vesicles fuse.
These findings offer a new explanation for the functional heterogeneity of synaptic vesicles (‘primed’ vs ‘superprimed’). By limiting the amount of synaptic vesicles that reside in a highly fusogenic state, tomosyns equalize neurotransmission during activity. This study also advances our understanding on how synapse function can be regulated by targeting the molecular machinery that releases neurotransmitters.
The paper can be found here: https://rdcu.be/dCvS8
Image credit: ‘fragment of vesicles’ by Rini Brakkee