Insulin Vesicle Release: Walk, Kiss, Pause ... Then Run

Guy A. Rutter 1 ,2 and Elaine V. Hill 1 1 Department of Biochemistry, School of Medical Sciences, University Walk University of Bristol, Bristol 2 Department of Cell Biology, Division of Medicine, Imperial College, London, United Kingdom g.a.rutter{at}bris.ac.uk The mechanisms by which insulin-containing dense core secretory vesicles approach and finally fuse with the plasma membrane are of considerable current interest: defects in these processes may be one of the contributing factors to Type 2 diabetes. In this review, we discuss the molecular mechanisms involved in vesicle trafficking within the pancreatic ß-cell and the mechanisms whereby these may be regulated. We then go on to describe recent evidence that suggests that vesicle fusion at the plasma membrane is a partly reversible process ("kiss and run" or "cavity recapture"). We propose that vesicles may participate in a exo-endocytotic cycle in which a proportion of those that have already undergone an interaction with the plasma membrane may exchange exocytotic machinery with maturing vesicles.