A Database of Drosophila Genes & Genomes

FB2013_03, released May 7th, 2013
 

Reference Report

Reference
Citation Lagow, R.D., Bao, H., Cohen, E.N., Daniels, R.W., Zuzek, A., Williams, W.H., Macleod, G.T., Sutton, R.B., Zhang, B. (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. (Export to RIS)
FlyBase ID FBrf0201324
Publication Type Research paper
PubMed ID 17341138
PubMed Abstract Both constitutive secretion and Ca(2+)-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.
DOI 10.1371/journal.pbio.0050072
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Secondary IDs FBrf0193002
Language of Publication English
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Publication Type Journal
Abbreviation PLoS Biol.
Title PLoS Biology
Publication Year 2003-
ISBN/ISSN 1545-7885 1544-9173
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