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A dual mechanism controlling the localization and function of exocytic v-SNAREs.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2003 Jul 22; Vol. 100 (15), pp. 9011-6. Date of Electronic Publication: 2003 Jul 09. - Publication Year :
- 2003
-
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-3 delta, 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.
- Subjects :
- Adaptor Protein Complex 3
Animals
Binding Sites
Cell Line
DNA-Binding Proteins metabolism
Dogs
Exocytosis
HeLa Cells
Humans
Membrane Proteins genetics
Membrane Proteins metabolism
Molecular Sequence Data
Peptide Fragments genetics
Peptide Fragments metabolism
R-SNARE Proteins
SNARE Proteins
Subcellular Fractions metabolism
Transcription Factors metabolism
Two-Hybrid System Techniques
Membrane Proteins physiology
Vesicular Transport Proteins
Subjects
Details
- Language :
- English
- ISSN :
- 0027-8424
- Volume :
- 100
- Issue :
- 15
- Database :
- MEDLINE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 12853575
- Full Text :
- https://doi.org/10.1073/pnas.1431910100