Abstract
The SNARE hypothesis proposes that membrane trafficking specificity is mediated by preferential high affinity interactions between particular v (vesicle membrane)- and t (target membrane)-SNARE combinations. The specificity of interactions among a diverse set of SNAREs, however, is unknown. We have tested the SNARE hypothesis by analyzing potential SNARE complexes between five proteins of the vesicle-associated membrane protein (VAMP) family, three members of the synaptosome-associated protein-25 (SNAP-25) family and three members of the syntaxin family. All of the 21 combinations of SNAREs tested formed stable complexes. Sixteen were resistant to SDS denaturation, and most complexes thermally denatured between 70 and 90 degreesC. These results suggest that the specificity of membrane fusion is not encoded by the interactions between SNAREs.
Highlights
From the Howard Hughes Medical Institute, Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, California 94305-5428
SNARE proteins belonging to the vesicle-associated membrane protein (VAMP), synaptosome-associated protein-25 (SNAP-25), and syntaxin families form heteromeric complexes that consist of extended, parallel four-helical bundles [9, 10]
There should be a sufficient number of SNARE proteins to account for constitutive membrane trafficking as well as the specialized and regulated secretory processes found in differentiated cell types
Summary
Vol 274, No 9, Issue of February 26, pp. 5649 –5653, 1999 Printed in U.S.A. Bin Yang‡, Lino Gonzalez, Jr.‡§, Rytis Prekeris, Martin Steegmaier, Raj J. Sixteen were resistant to SDS denaturation, and most complexes thermally denatured between 70 and 90 °C These results suggest that the specificity of membrane fusion is not encoded by the interactions between SNAREs. Membrane compartments in eukaryotic cells are in constant dynamic flux. The number and localization of SNARE proteins suggest that high affinity interactions between sets of SNAREs could account for aspects of the specificity of membrane organization. Every combination that included a syntaxin, VAMP, and SNAP-25 family member formed a highly stable SNARE complex. These results suggest that the core interactions between SNAREs are not the source of specificity in membrane trafficking
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