Biophysical Society Thematic Meeting| Padova 2019

Quantitative Aspects of Membrane Fusion and Fission

Thursday Speaker Abstracts

NEED FOR SPEED: DYNAMIC NANOCLUSTERING AND UNCLUSTERING OF MUNC18/SYNTAXIN-1 DURING EXOCYTOSIS Frederic A. Meunier ; 1 The University of Queensland, Queensland Brain Institute, Brisbane, Queensland, Australia Communication between cells relies on regulated exocytosis, a multi-step process that involves the docking, priming and fusion of secretory vesicles with the plasma membrane, culminating in the release of neurotransmitters and hormones. Key proteins and lipids involved in exocytosis are subjected to Brownian movement and constantly switch between distinct motion states which are governed by short-lived molecular interactions. Critical biochemical reactions that occur in the confinement of nanodomains, underpin the precise sequence of priming steps which leads to the fusion reaction. The advent of super-resolution microscopy techniques has provided the means to visualize individual molecules on the plasma membrane of live cells with high spatio-temporal resolution. I will discuss the result of our recent studies revealing a highly dynamic nature of the nanoscale organization of the exocytic machinery. I will particularly focus on the mechanisms regulating soluble N-ethylmaleimide sensitive-factor attachment receptor (SNARE) syntaxin- 1 nanoclustering in motor nerve terminals (Bademosi et al., 2017, 2018) and neurosecretory cells (Kasula et al., 2016). References: Bademosi, A. T., et al., 2017. In vivo single-molecule imaging of syntaxin1A reveals polyphosphoinositide- and activity-dependent trapping in presynaptic nanoclusters. Nat. Commun. 8, 13660.Bademosi, A. T., et al., 2018. Trapping of syntaxin1a in presynaptic nanoclusters by a clinically relevant general anesthetic. Cell Rep. 22, 427- 440.Kasula, R., et al., 2016. The Munc18-1 domain 3a hinge-loop controls syntaxin-1A nanodomain assembly and engagement with the SNARE complex during secretory vesicle priming. J. Cell Biol., 201508118.

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