In:
eLife, eLife Sciences Publications, Ltd, Vol. 6 ( 2017-05-06)
Abstract:
Nerve cells communicate with other nerve cells by releasing small molecules called neurotransmitters. The neurotransmitters are first packaged inside bubble-like structures called vesicles, which fuse with the membrane of the nerve cell when it is stimulated. Once the vesicle and membrane have fused, the neurotransmitters are released outside the nerve cell and are detected when they bind to proteins on the surface of other nearby nerve cells. A machinery of different proteins controls membrane fusion. Amongst these proteins are five called Munc18-1, Munc13-1, syntaxin-1, synaptobrevin and SNAP-25. The last three form a tight bundle called SNARE complex that brings the vesicle and cell membrane together and is essential for the two to fuse. Munc18-1 and Munc13-1 orchestrate the assembly of the SNARE complex. Previous studies suggested that Munc18-1 binds to synaptobrevin, providing a template to bring syntaxin-1 and synaptobrevin together and thereby helping the SNARE complex to form. However, the importance of the interaction between Munc18-1 and synaptobrevin was not clearly established, and it was not known how Munc13-1 is involved. Sitarska, Xu et al. have now measured how mutated versions of Munc18-1 bind to synaptobrevin and tested how the mutations affect membrane fusion. A mutation in Munc18-1 that increased binding to synaptobrevin increased membrane fusion too, while a mutation that decreased binding had the opposite effect and reduced fusion. The results support the idea that Munc18-1 provides a template for the SNARE complex to form. One mutation stimulated Munc18-1 so that Munc13-1 was no longer needed for fusion when the mutant Munc18-1 was tested in fusion assays with artificial membranes. This mutation was designed to perturb the structure of a region of Munc18-1 protein that normally inhibits the binding of synaptobrevin. These results suggest that by adopting a state where it cannot bind synaptobrevin, Munc18-1 can only be stimulated to form the SNARE complex and trigger release of neurotransmitter when Munc13-1 is present. This provides a way for Munc13-1, which is regulated by many factors, to fine-tune the release of neurotransmitter. Future work will test whether these proteins work in the same way in living animals. This will help us understand how communication between neurons is finely controlled to enable the brain to carry out its many different tasks.
Type of Medium:
Online Resource
ISSN:
2050-084X
DOI:
10.7554/eLife.24278.001
DOI:
10.7554/eLife.24278.002
DOI:
10.7554/eLife.24278.003
DOI:
10.7554/eLife.24278.004
DOI:
10.7554/eLife.24278.005
DOI:
10.7554/eLife.24278.006
DOI:
10.7554/eLife.24278.007
DOI:
10.7554/eLife.24278.008
DOI:
10.7554/eLife.24278.009
DOI:
10.7554/eLife.24278.010
DOI:
10.7554/eLife.24278.011
DOI:
10.7554/eLife.24278.012
DOI:
10.7554/eLife.24278.013
DOI:
10.7554/eLife.24278.014
DOI:
10.7554/eLife.24278.015
DOI:
10.7554/eLife.24278.016
DOI:
10.7554/eLife.24278.017
DOI:
10.7554/eLife.24278.018
DOI:
10.7554/eLife.24278.019
DOI:
10.7554/eLife.24278.020
DOI:
10.7554/eLife.24278.021
Language:
English
Publisher:
eLife Sciences Publications, Ltd
Publication Date:
2017
detail.hit.zdb_id:
2687154-3