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

Latrotoxin receptor signaling engages the UNC-13-dependent vesicle-priming pathway in C. elegans
Latrotoxin receptor signaling engages the UNC-13-dependent vesicle-priming pathway in C. elegans
?-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.
0960-9822
1374-1379
Willson, J.
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Amliwala, K.
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Davis, A.
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Cook, A.
33202006-e56a-44ee-9f85-dfacb9c7602e
Cuttle, M.F.
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Kriek, N.
2be7a156-d337-4337-bf8d-5e782d87d8df
Hopper, N.A.
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Connor, V.
bc8fea0c-2bd2-48a3-8ca6-e747ffd6298d
Harder, A.
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Walker, R.J.
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Holden-Dye, L.
8032bf60-5db6-40cb-b71c-ddda9d212c8e
Willson, J.
3fe4cbeb-fd6f-4e81-af4f-3b753e358e5c
Amliwala, K.
e71463eb-6480-4395-8e2a-57a005809be8
Davis, A.
72a3a591-f100-4c7a-b772-fb2f7a77c3fb
Cook, A.
33202006-e56a-44ee-9f85-dfacb9c7602e
Cuttle, M.F.
f6409ed2-0472-4da8-a533-e8d94fb7b065
Kriek, N.
2be7a156-d337-4337-bf8d-5e782d87d8df
Hopper, N.A.
ddc67e10-c632-4400-9b27-a93de6baabd7
Connor, V.
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Harder, A.
0cf8ea99-09fd-416c-ab07-4c7f4d63d44c
Walker, R.J.
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Holden-Dye, L.
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Willson, J., Amliwala, K., Davis, A., Cook, A., Cuttle, M.F., Kriek, N., Hopper, N.A., 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 (24), 1374-1379. (doi:10.1016/j.cub.2004.07.056).

Record type: Article

Abstract

?-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.

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Submitted date: 14 October 2003
Published date: 10 August 2004

Identifiers

Local EPrints ID: 26178
URI: http://eprints.soton.ac.uk/id/eprint/26178
ISSN: 0960-9822
PURE UUID: c0784294-9ac0-4ba8-ac49-4f1be7d82787
ORCID for R.J. Walker: ORCID iD orcid.org/0000-0002-9031-7671
ORCID for L. Holden-Dye: ORCID iD orcid.org/0000-0002-9704-1217

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Date deposited: 25 Apr 2006
Last modified: 09 Jan 2022 04:04

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Contributors

Author: J. Willson
Author: K. Amliwala
Author: A. Davis
Author: A. Cook
Author: M.F. Cuttle
Author: N. Kriek
Author: N.A. Hopper
Author: V. Connor
Author: A. Harder
Author: R.J. Walker ORCID iD
Author: L. Holden-Dye ORCID iD

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