A dual mechanism controlling the localization and function of exocytic v-SNAREs

Sonia Martinez-Arca, Rachel Rudge, Marcella Vacca, Graça Raposo, Jacques Camonis, Véronique Proux-Gillardeaux, Laurent Daviet, Etienne Formstecher, Alexandre Hamburger, Francesco Filippini, Maurizio D'Esposito, Thierry Galli

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)9011-9016
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume100
Issue number15
DOIs
Publication statusPublished - Jul 22 2003

ASJC Scopus subject areas

  • Genetics
  • General

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