The tail domain of tomosyn controls membrane fusion through tomosyn displacement by VAMP2

Biochemical and Biophysical Research Communications
Yasunori YamamotoT Sakisaka

Abstract

Neurotransmitter release is regulated by SNARE complex-mediated synaptic vesicle fusion. Tomosyn sequesters target SNAREs (t-SNAREs) through its C-terminal VAMP-like domain (VLD). Cumulative biochemical results suggest that the tomosyn-SNARE complex is so tight that VAMP2 cannot displace tomosyn. Based on these results, the tomosyn-SNARE complex has been believed to be a dead-end complex to inhibit neurotransmitter release. On the other hand, some studies using siRNA depletion of tomosyn suggest that tomosyn positively regulates exocytosis. Therefore, it is still controversial whether tomosyn is a simple inhibitor for neurotransmitter release. We recently reported that the inhibitory activity of tomosyn is regulated by the tail domain binding to the VLD. In this study, we employed the liposome fusion assay in order to further understand modes of action of tomosyn in detail. The tail domain unexpectedly had no effect on binding of the VLD to t-SNARE-bearing liposomes. Nonetheless, the tail domain decreased the inhibitory activity of the VLD on the SNARE complex-mediated liposome fusion. These results indicate that the tail domain controls membrane fusion through tomosyn displacement by VAMP2. Deletion of the tail domain-binding ...Continue Reading

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Citations

Oct 28, 2010·The Journal of Biological Chemistry·Yasunori YamamotoToshiaki Sakisaka
Feb 19, 2011·The Journal of Biological Chemistry·Antionette L WilliamsEdward L Stuenkel
Mar 13, 2014·PloS One·Cornelia J GeertsAlexander J A Groffen
Sep 23, 2014·The Journal of Clinical Investigation·Qiuyu ZhuCharles J Lowenstein
Jan 27, 2015·Traffic·Devon C Crawford, Ege T Kavalali
Apr 20, 2014·Brain Structure & Function·Cornelia J GeertsAlexander J A Groffen
Sep 8, 2016·Proceedings of the National Academy of Sciences of the United States of America·Feng LiFrederic Pincet
Jul 27, 2017·PloS One·Cornelia J GeertsAlexander J A Groffen
Apr 3, 2021·Frontiers in Cell and Developmental Biology·Gaël MénaschéUlrich Blank
Aug 24, 2021·Frontiers in Molecular Neuroscience·Chad W Sauvola, J Troy Littleton

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