SNARE interactions are not selective - Implications for membrane fusion specificity

The SNARE hypothesis proposes that membrane trafficking specificity is medi ated by preferential high affinity interactions between particular v (vesic le membrane)- and t (target membrane)-SNARE combinations. The specificity o f 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, thr ee members of the synaptosome-associated protein-25 (SNAP-25) family and th ree members of the syntaxin family, All of the 21 combinations of SNAREs te sted formed stable complexes, Sixteen were resistant to SDS denaturation, a nd most complexes thermally denatured between 70 and 90 degrees C, These re sults suggest that the specificity of membrane fusion is not encoded by the interactions between SNAREs.