Neurotransmitter release mechanisms studied in Caenorhabditis elegans

Cell Calcium ◽  
2012 ◽  
Vol 52 (3-4) ◽  
pp. 289-295 ◽  
Author(s):  
Jeff W. Barclay ◽  
Alan Morgan ◽  
Robert D. Burgoyne
2012 ◽  
Vol 7 (7) ◽  
pp. 1351-1365 ◽  
Author(s):  
Andrea Burgalossi ◽  
SangYong Jung ◽  
Kwun-nok Mimi Man ◽  
Ramya Nair ◽  
Wolf J Jockusch ◽  
...  

2012 ◽  
Vol 47 (2) ◽  
pp. 188-197 ◽  
Author(s):  
Kopal Saharia ◽  
Upasna Arya ◽  
Ranjeet Kumar ◽  
Rashmi Sahu ◽  
Chinmaya Kumar Das ◽  
...  

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Ewa Sitarska ◽  
Junjie Xu ◽  
Seungmee Park ◽  
Xiaoxia Liu ◽  
Bradley Quade ◽  
...  

Munc18-1 orchestrates SNARE complex assembly together with Munc13-1 to mediate neurotransmitter release. Munc18-1 binds to synaptobrevin, but the relevance of this interaction and its relation to Munc13 function are unclear. NMR experiments now show that Munc18-1 binds specifically and non-specifically to synaptobrevin. Specific binding is inhibited by a L348R mutation in Munc18-1 and enhanced by a D326K mutation designed to disrupt the ‘furled conformation’ of a Munc18-1 loop. Correspondingly, the activity of Munc18-1 in reconstitution assays that require Munc18-1 and Munc13-1 for membrane fusion is stimulated by the D326K mutation and inhibited by the L348R mutation. Moreover, the D326K mutation allows Munc13-1-independent fusion and leads to a gain-of-function in rescue experiments in Caenorhabditis elegans unc-18 nulls. Together with previous studies, our data support a model whereby Munc18-1 acts as a template for SNARE complex assembly, and autoinhibition of synaptobrevin binding contributes to enabling regulation of neurotransmitter release by Munc13-1.


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