A second SARE role for exocytic SNAP25 in endosome fusion

Department of Biochemistry, University of Wisconsin, Madison, WI 53706, USA.
Molecular Biology of the Cell (Impact Factor: 4.47). 06/2006; 17(5):2113-24. DOI: 10.1091/mbc.E06-01-0074
Source: PubMed


Soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins play key roles in membrane fusion, but their sorting to specific membranes is poorly understood. Moreover, individual SNARE proteins can function in multiple membrane fusion events dependent upon their trafficking itinerary. Synaptosome-associated protein of 25 kDa (SNAP25) is a plasma membrane Q (containing glutamate)-SNARE essential for Ca2+-dependent secretory vesicle-plasma membrane fusion in neuroendocrine cells. However, a substantial intracellular pool of SNAP25 is maintained by endocytosis. To assess the role of endosomal SNAP25, we expressed botulinum neurotoxin E (BoNT E) light chain in PC12 cells, which specifically cleaves SNAP25. BoNT E expression altered the intracellular distribution of SNAP25, shifting it from a perinuclear recycling endosome to sorting endosomes, which indicates that SNAP25 is required for its own endocytic trafficking. The trafficking of syntaxin 13 and endocytosed cargo was similarly disrupted by BoNT E expression as was an endosomal SNARE complex comprised of SNAP25/syntaxin 13/vesicle-associated membrane protein 2. The small-interfering RNA-mediated down-regulation of SNAP25 exerted effects similar to those of BoNT E expression. Our results indicate that SNAP25 has a second function as an endosomal Q-SNARE in trafficking from the sorting endosome to the recycling endosome and that BoNT E has effects linked to disruption of the endosome recycling pathway.

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    • "The heavy chain of the toxin has a high affinity for the membrane receptors and, once bound, BTA undergoes endocytosis. The light chain is released within the cell, where it acts as a zinc-dependent endoprotease [16] [17] [18]. "
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    Evidence-based Complementary and Alternative Medicine 02/2013; 2013(1):381459. DOI:10.1155/2013/381459 · 1.88 Impact Factor
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    • "If so, then SNAP23CΔ9 would be expected to be a more potent inhibitor of cell motility than other soluble SNARE domains, as was observed. In support of this model, others have reported that a VAMP2-syntaxin13-SNAP25 complex mediates traffic from a sorting endosome to a recycling endosome in neurons [18,36]. In non-neuronal cells, a similar complex, such as the VAMP3-syntaxin13-SNAP23 complex described here, may be involved in an analogous trafficking pathway. "
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    BMC Cell Biology 08/2010; 11(1):62. DOI:10.1186/1471-2121-11-62 · 2.34 Impact Factor
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    • "As GLUT4 molecules appear to be recruited at random it is tempting to speculate that upon low-level insulin stimulation, GLUT4 molecules are mobilized by the action of a downstream insulin effector on a protein or membrane structure that directly regulates GLUT4 retention. The result would be the release of GLUT4 molecules from the GSC into the GLUT4 cell surface recycling pathway or the release of GSVs to allow them to fuse with the plasma membrane (via the formation of the syntaxin 4/ SNAP23/VAMP2 SNARE complex [22]) or perhaps with another compartment of the GLUT4 cell surface recycling pathway (i.e., via a syntaxin 13/SNAP23/VAMP2 complex [23] [24]). In any case, this insulin effector would be the rate-limiting factor in GLUT4 mobilization and affect (a limited amount of) components of the retention mechanism or GSVs at a random fashion. "
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