Abstract
SNARE [soluble NSF ( N -ethylmaleimide-sensitive factor) attachment protein receptor] proteins are essential for membrane fusion but their regulation is not yet fully understood. We have previously shown that the amino-terminal Longin domain of the v-SNARE TI-VAMP (tetanus neurotoxin-insensitive vesicle-associated membrane protein)/VAMP7 plays an inhibitory role in neurite outgrowth. The goal of this study was to investigate the regulation of TI-VAMP as a model of v-SNARE regulation. We show here that the Longin domain (LD) plays a dual role. First, it negatively regulates the ability of TI-VAMP and of a Longin/Synaptobrevin chimera to participate in SNARE complexes. Second, it interacts with the adaptor complex AP-3 and this interaction targets TI-VAMP to late endosomes. Accordingly, in mocha cells lacking AP-3δ, TI-VAMP is retained in an early endosomal compartment. Furthermore, TI-VAMPc, an isoform of TI-VAMP lacking part of the LD, does not interact with AP-3, and therefore is not targeted to late endosomes; however, this shorter LD still inhibits SNARE-complex formation. These findings support a mechanism controlling both localization and function of TI-VAMP through the LD and clathrin adaptors. Moreover, they point to the amino-terminal domains of SNARE proteins as multifunctional modules responsible for the fine tuning of SNARE function.
Bibliography
Martinez-Arca, S., Rudge, R., Vacca, M., Raposo, G., Camonis, J., Proux-Gillardeaux, V., Daviet, L., Formstecher, E., Hamburger, A., Filippini, F., DâEsposito, M., & Galli, T. (2003). A dual mechanism controlling the localization and function of exocytic v-SNAREs. Proceedings of the National Academy of Sciences, 100(15), 9011â9016.
Authors
12
- Sonia Martinez-Arca (first)
- Rachel Rudge (additional)
- Marcella Vacca (additional)
- Graça Raposo (additional)
- Jacques Camonis (additional)
- Véronique Proux-Gillardeaux (additional)
- Laurent Daviet (additional)
- Etienne Formstecher (additional)
- Alexandre Hamburger (additional)
- Francesco Filippini (additional)
- Maurizio D'Esposito (additional)
- Thierry Galli (additional)
References
39
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Dates
Type | When |
---|---|
Created | 22 years, 1 month ago (July 22, 2003, 3:39 p.m.) |
Deposited | 3 years, 4 months ago (April 25, 2022, 9:29 p.m.) |
Indexed | 1 month, 1 week ago (July 19, 2025, 11:46 p.m.) |
Issued | 22 years, 1 month ago (July 9, 2003) |
Published | 22 years, 1 month ago (July 9, 2003) |
Published Online | 22 years, 1 month ago (July 9, 2003) |
Published Print | 22 years, 1 month ago (July 22, 2003) |
@article{Martinez_Arca_2003, title={A dual mechanism controlling the localization and function of exocytic v-SNAREs}, volume={100}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.1431910100}, DOI={10.1073/pnas.1431910100}, number={15}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Martinez-Arca, Sonia and Rudge, Rachel and Vacca, Marcella and Raposo, Graça and Camonis, Jacques and Proux-Gillardeaux, Véronique and Daviet, Laurent and Formstecher, Etienne and Hamburger, Alexandre and Filippini, Francesco and D’Esposito, Maurizio and Galli, Thierry}, year={2003}, month=jul, pages={9011–9016} }