Organisation of membrane proteins and lipids during exocytosis and endocytosis
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Meunier, Frederic A
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Cristino, Alexandre
Wood, Stephen A
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Abstract
The plasma membrane is a vital cellular structure providing the interface for cells to either send or receive vital signals to and from their environments respectively. Exocytosis is the mechanism by which secretory vesicles fuse with the plasma membrane to release their contents into the extracellular space. This mechanism underpins neuronal communication through the release of neurotransmitters. In response to vesicular fusion, the plasma membrane responds promptly by retrieving an equal surface of the plasma membrane back into the cell by inward invagination and fission, a process called compensatory endocytosis. Exo- and endocytosis is invariably linked and tight regulation of the organisation of the plasma membrane is required to facilitate these coupled mechanisms with nanosecond precision. Exocytosis relies on a set of key proteins, primarily, soluble N-ethylmaleimide sensitive-factor attachment receptor (SNARE) proteins, syntaxin1, SNAP-25 found at the plasma membrane and VAMP2 found at the vesicle membrane. Their formation into the SNARE complex, critical for synaptic vesicle fusion with the synaptic vesicle membrane, is controlled by a set of accessory proteins including Munc18-1 and the actin cytoskeleton. Recent advances in microscopy approaches have allowed us to investigate the spatiotemporal dynamics of key proteins behaviour during exo and endocytosis with increasing resolution. More specifically, the goal of this thesis is to elucidate the contribution of various synaptic proteins at the plasma membrane during exo- and endocytosis, with particular emphasis the remodelling of the actin cytoskeleton and the plasma membrane. This thesis comprises a set of published works under the theme of neuroscience, cell biology and microscopy approaches to uncover the role of key proteins in exocytosis and endocytosis. My contribution to the field is evidenced by three peer-reviewed papers that uncover the roles of key accessory proteins, Dynamin, Munc-18-1 and signalling receptors that promote plasma membrane and cytoskeletal remodelling. The development of advanced microscopy technologies and analysis methods throughout this thesis have provided a solid framework on which to uncover the nanoscale dynamics of exo- and endocytic processes.
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Thesis (Professional Doctorate)
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Doctor of Philosophy (PhD)
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School of Environment and Sc
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The author owns the copyright in this thesis, unless stated otherwise.
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Subject
plasma membrane
actin cytoskeleton
exocytosis
endocytosis
neuronal communication