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Matthijs Verhage"Trafficking, docking and release of secretory vesicles"

Abstract :


Most cells contain a variety of transport vesicles traveling to different destinations.
Formation of SNARE complexes between vesicle and target membrane is a central aspect of the final fusion reaction in most intracellular routes. The regulation of SNARE-complex formation and -function is a central element in tuning intercellular communication, for instance in synapses. We study the molecular mechanisms that orchestrate trafficking, docking and secretion of secretory vesicles using molecular genetic tools, life cell imaging, electrophysiology, evanescent field microscopy (TIRFM) and electron microscopy in chromaffin cells and neurons. We have characterized the minimal machinery that docks secretory vesicles at the target membrane and conclude that the protein Munc18-1 renders syntaxin-1/SNAP-25 acceptor complexes at the target membrane receptive for vesicular synaptotagmin-1 to dock secretory vesicles. Furthermore, we have identified a new family of C2-domain containing proteins, the Doc2 family, to drive spontaneous fusion events in neurons. Finally, we have characterized trafficking and recruitment of secretory vesicles in neurons using GFP- and superecliptic pHluorin-tagged cargo. In this talk, I will present the main data that led to these conclusions and propose a model that can account for most of the literature on vesicle trafficking, docking and fusion. In addition, data will be presented on the role of additional genes, modulation by protein phosphorylation and cytoskeletal components to regulate vesicle docking at the target, the availability of fusion-competent vesicles and activity dependent adaptations in these processes.

Selected publications

Mohrmann et al. (2010) Science 330:502-5
Groffen et al. (2010) Science 327:1614-8
de Wit et al. (2009) Cell 138:935-46
Gerber et al. (2008) Science 321:1507-10
Wierda et al. (2007) Neuron 54:275-90

Christophe Mulle