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dc.creatorLagow, Robert Den
dc.creatorBao, Hongen
dc.creatorCohen, Evan Nen
dc.creatorDaniels, Richard Wen
dc.creatorZuzek, Aleksejen
dc.creatorWilliams, Wade Hen
dc.creatorMacleod, Gregory Ten
dc.creatorSutton, R. Bryanen
dc.creatorZhang, Bingen
dc.identifier.citationLagow RD, Bao H, Cohen EN, Daniels RW, Zuzek A, et al. (2007) Modification of a Hydrophobic Layer by a Point Mutation in Syntaxin 1A Regulates the Rate of Synaptic Vesicle Fusion. PLoS Biol 5(4): e72. doi:10.1371/journal.pbio.0050072en
dc.description.abstractBoth constitutive secretion and Ca2+-regulated exocytosis require the assembly of the soluble N-ethylmaleimide–sensitive factor attachment protein receptor (SNARE) complexes. At present, little is known about how the SNARE complexes mediating these two distinct pathways differ in structure. Using the Drosophila neuromuscular synapse as a model, we show that a mutation modifying a hydrophobic layer in syntaxin 1A regulates the rate of vesicle fusion. Syntaxin 1A molecules share a highly conserved threonine in the C-terminal +7 layer near the transmembrane domain. Mutation of this threonine to isoleucine results in a structural change that more closely resembles those found in syntaxins ascribed to the constitutive secretory pathway. Flies carrying the I254 mutant protein have increased levels of SNARE complexes and dramatically enhanced rate of both constitutive and evoked vesicle fusion. In contrast, overexpression of the T254 wild-type protein in neurons reduces vesicle fusion only in the I254 mutant background. These results are consistent with molecular dynamics simulations of the SNARE core complex, suggesting that T254 serves as an internal brake to dampen SNARE zippering and impede vesicle fusion, whereas I254 favors fusion by enhancing intermolecular interaction within the SNARE core complex.en
dc.description.sponsorshipThis research was supported by a start-up fund from the University of Texas at Austin and in part by a Career Award from the National Science Foundation and a National Institutes of Health (NIH)/National Institute of Environmental Health Sciences grant (to BZ), by Undergraduate Research Awards (to ENC and RWD), and in part by a grant from NIH and in part by a Career Award in Biomedical Sciences from the Burroughs-Wellcome Fund (to RBS).en
dc.publisherPublic Library of Scienceen
dc.rightsAttribution 3.0 United Statesen
dc.subjectAction potentialsen
dc.subjectSynaptic vesiclesen
dc.subjectVesicle fusionen
dc.titleModification of a Hydrophobic Layer by a Point Mutation in Syntaxin 1A Regulates the Rate of Synaptic Vesicle Fusionen
dc.description.departmentBiological Sciences, School ofen

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Attribution 3.0 United States
Except where otherwise noted, this item's license is described as Attribution 3.0 United States