Structural and evolutionary studies on the vesicle fusion machinery
The mechanism by which eukaryotic cells transport material between intracellular organelles is of fundamental importance in cell biology. Transport is mediated by vesicles that bud from a donor organelle and afterwards fuse with a target organelle. As each of the internal compartments serves a specific and vital cellular function, it must maintain its identity during vesicle trafficking. This is achieved by specific protein machineries that tightly regulate each transport step. The complicated protein network that catalyzes the docking and fusion of vesicles is best studied for the process of neuronal exocytosis. The core of the neuronal release machinery is composed of the SNARE proteins syntaxin 1, SNAP-25, and synaptobrevin that are thought to zipper into a tight complex between the synaptic vesicle and plasma membrane. The central SNARE fusion machinery is regulated by a variety of other factors.
Our primary goal is, by combining a variety of biophysical, structural, and bioinformatic approaches, to embark on a detailed molecular description of the protein-protein interactions of the membrane fusion machinery, in particular of the one involved in neurosecretion. In addition, we intend to correlate the in vitro SNARE activity with secretory phases. Furthermore, we plan to investigate the conservation of other SNARE sets involved in intracellular trafficking steps. Moreover, we want to study the structural and functional conservation of factors that control and organize the central SNARE machinery. Finally, it is planned to study the evolution of the neurosecretory apparatus morphologically in different organisms.