Mechanism of arachidonic acid action on syntaxin-Munc18

Emma Connell, Frédéric Darios, Kerensa Broersen, Naomi Gatsby, Sew-Yeu Peak-Chew, Colin Rickman, Bazbek Davletov

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64 Citations (Scopus)

Abstract

Syntaxin and Munc18 are, in tandem, essential for exocytosis in all eukaryotes. Recently, it was shown that Munc18 inhibition of neuronal syntaxin 1 can be overcome by arachidonic acid, indicating that this common second messenger acts to disrupt the syntaxin-Munc18 interaction. Here, we show that arachidonic acid can stimulate syntaxin 1 alone, indicating that it is syntaxin 1 that undergoes a structural change in the syntaxin 1-Munc18 complex. Arachidonic acid is incapable of dissociating Munc18 from syntaxin 1 and, crucially, Munc18 remains associated with syntaxin 1 after arachidonic-acid-induced syntaxin 1 binding to synaptosomal-associated protein 25 kDa (SNAP25). We also show that the same principle operates in the case of the ubiquitous syntaxin 3 isoform, highlighting the conserved nature of the mechanism of arachidonic acid action. Neuronal soluble N-ethyl maleimide sensitive factor attachment protein receptors (SNAREs) can be isolated from brain membranes in a complex with endogenous Munc18, consistent with a proposed function of Munc18 in vesicle docking and fusion.
Original languageEnglish
Pages (from-to)414-9
Number of pages6
JournalEMBO Reports
Volume8
Issue number4
DOIs
Publication statusPublished - 2007

Keywords

  • Amino Acid Sequence
  • Animals
  • Arachidonic Acid
  • Brain Chemistry
  • Cell Membrane
  • Dissociative Disorders
  • Molecular Sequence Data
  • Munc18 Proteins
  • Protein Interaction Mapping
  • Qa-SNARE Proteins
  • Rats
  • SNARE Proteins
  • Synaptosomal-Associated Protein 25
  • Syntaxin 1

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    Connell, E., Darios, F., Broersen, K., Gatsby, N., Peak-Chew, S-Y., Rickman, C., & Davletov, B. (2007). Mechanism of arachidonic acid action on syntaxin-Munc18. EMBO Reports, 8(4), 414-9. https://doi.org/10.1038/sj.embor.7400935