Protein-protein interactions involving Munc18 in regulated exocytosis

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Neurons, endocrine and many other cell types communicate with one another and other tissues in a co-ordinated manner by the tightly regulated release of transmitters and signalling molecules. Transmitters are packaged into small lipid vesicles which have to fuse with the cell membrane to release their contents only at the appropriate time and place. Most of the individual parts of the machinery inside the cell that allows this to occur have been discovered over the past ten years but we still have a very limited understanding of how the process works and how it is regulated. Changes in the functioning of the machinery for release are believed to contribute to learning and memory and affect behaviour. We aim to investigate in detail one essential component of the machinery, Munc18-1, by making specific modifications to its structure. This will allow us to learn how its interactions with other components contribute to its function in the various steps leading to transmitter release.