Mechanism of arachidonic acid action on syntaxin-Munc18

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

Research output: Contribution to journalArticle

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

Fingerprint

Syntaxin 1
Qa-SNARE Proteins
Arachidonic Acid
Synaptosomal-Associated Protein 25
Exocytosis
Second Messenger Systems
Eukaryota
Protein Isoforms
Membranes
Brain

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

Cite this

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
Connell, Emma ; Darios, Frédéric ; Broersen, Kerensa ; Gatsby, Naomi ; Peak-Chew, Sew-Yeu ; Rickman, Colin ; Davletov, Bazbek. / Mechanism of arachidonic acid action on syntaxin-Munc18. In: EMBO Reports. 2007 ; Vol. 8, No. 4. pp. 414-9.
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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, vol. 8, no. 4, pp. 414-9. https://doi.org/10.1038/sj.embor.7400935

Mechanism of arachidonic acid action on syntaxin-Munc18. / Connell, Emma; Darios, Frédéric; Broersen, Kerensa; Gatsby, Naomi; Peak-Chew, Sew-Yeu; Rickman, Colin; Davletov, Bazbek.

In: EMBO Reports, Vol. 8, No. 4, 2007, p. 414-9.

Research output: Contribution to journalArticle

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AU - Connell, Emma

AU - Darios, Frédéric

AU - Broersen, Kerensa

AU - Gatsby, Naomi

AU - Peak-Chew, Sew-Yeu

AU - Rickman, Colin

AU - Davletov, Bazbek

PY - 2007

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KW - Molecular Sequence Data

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KW - Qa-SNARE Proteins

KW - Rats

KW - SNARE Proteins

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KW - Syntaxin 1

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JO - EMBO Reports

JF - EMBO Reports

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