دورية أكاديمية
Trapping of Syntaxin1a in Presynaptic Nanoclusters by a Clinically Relevant General Anesthetic
| العنوان: | Trapping of Syntaxin1a in Presynaptic Nanoclusters by a Clinically Relevant General Anesthetic |
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| المؤلفون: | Bademosi, Adekunle T., Steeves, James, Karunanithi, Shanker, Zalucki, Oressia H, Gormal, Rachel S, Liu, Shu, Lauwers, Elsa, Verstreken, Patrik, Anggono, Victor, Meunier, Frederic A, van Swinderen, Bruno |
| بيانات النشر: | Elsevier |
| سنة النشر: | 2018 |
| المجموعة: | The University of Queensland: UQ eSpace |
| مصطلحات موضوعية: | Drosophila melanogaster, PC12, SNAP-25, SNARE, etomidate, neurotransmission, propofol, sptPALM, super-resolution microscopy, syntaxin1A, 1300 Biochemistry, Genetics and Molecular Biology |
| الوصف: | Propofol is the most commonly used general anesthetic in humans. Our understanding of its mechanism of action has focused on its capacity to potentiate inhibitory systems in the brain. However, it is unknown whether other neural mechanisms are involved in general anesthesia. Here, we demonstrate that the synaptic release machinery is also a target. Using single-particle tracking photoactivation localization microscopy, we show that clinically relevant concentrations of propofol and etomidate restrict syntaxin1A mobility on the plasma membrane, whereas non-anesthetic analogs produce the opposite effect and increase syntaxin1A mobility. Removing the interaction with the t-SNARE partner SNAP-25 abolishes propofol-induced syntaxin1A confinement, indicating that syntaxin1A and SNAP-25 together form an emergent drug target. Impaired syntaxin1A mobility and exocytosis under propofol are both rescued by co-expressing a truncated syntaxin1A construct that interacts with SNAP-25. Our results suggest that propofol interferes with a step in SNARE complex formation, resulting in non-functional syntaxin1A nanoclusters. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| تدمد: | 2211-1247 |
| العلاقة: | orcid:0000-0001-5157-8572; orcid:0000-0002-4267-9491; orcid:0000-0003-1604-0253; orcid:0000-0002-4062-4884; orcid:0000-0001-6400-1107; APP1103923; LE0882864; LE130100078; DP170100125; DP1093968 |
| الإتاحة: | https://doi.org/10.1016/j.celrep.2017.12.054Test https://espace.library.uq.edu.au/view/UQ:716280Test |
| رقم الانضمام: | edsbas.81B037B2 |
| قاعدة البيانات: | BASE |
Full Text Finder | تدمد: | 22111247 |
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