Latrotoxin receptor signaling engages the UNC-13-dependent vesicle-priming pathway in C. elegans

Willson, J., Amliwala, K., Davis, A., Cook, A., Cuttle, M.F., Kriek, N., Hopper, N.A., O'Connor, V., Harder, A., Walker, R.J. and Holden-Dye, L. (2004) Latrotoxin receptor signaling engages the UNC-13-dependent vesicle-priming pathway in C. elegans Current Biology, 14, (15), pp. 1374-1379. (doi:10.1016/j.cub.2004.07.056).


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?-latrotoxin (LTX), a 120 kDa protein in black widow spider venom, triggers massive neurotransmitter exocytosis. Previous studies have highlighted a role for both intrinsic pore-forming activity and receptor binding in the action of this toxin. Intriguingly, activation of a presynaptic G protein-coupled receptor, latrophilin, may trigger release independent of pore-formation. Here we have utilized a previously identified ligand of nematode latrophilin, emodepside, to define a latrophilin-dependent pathway for neurotransmitter release in C. elegans. In the pharyngeal nervous system of this animal, emodepside (100 nM) stimulates exocytosis and elicits pharyngeal paralysis. The pharynxes of animals with latrophilin (lat-1) gene knockouts are resistant to emodepside, indicating that emodepside exerts its high-affinity paralytic effect through LAT-1. The expression pattern of lat-1 supports the hypothesis that emodepside exerts its effect on the pharynx primarily via neuronal latrophilin. We build on these observations to show that pharynxes from animals with either reduction or loss of function mutations in Gq, phospholipaseC-?, and UNC-13 are resistant to emodepside. The latter is a key priming molecule essential for synaptic vesicle-mediated release of neurotransmitter. We conclude that the small molecule ligand emodepside triggers latrophilin-mediated exocytosis via a pathway that engages UNC-13-dependent vesicle priming.

Item Type: Article
Digital Object Identifier (DOI): doi:10.1016/j.cub.2004.07.056
ISSNs: 0960-9822 (print)
Related URLs:
ePrint ID: 26178
Date :
Date Event
14 October 2003Submitted
10 August 2004Published
Date Deposited: 25 Apr 2006
Last Modified: 16 Apr 2017 22:34
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