Molecular Controls On Regulated Neurotransmitter And Neurohormone Secretion

The neurosecretion of chemical messengers via Ca2+-dependent exocytosis is fundamental to the survival of multicellular organisms and to the induction of physiological changes that may underlie learning and behavior. These processes involve ensembles of molecular interactions or `nanomachines', which continuously modulate vesicle cycling and membrane fusion. The formation and disassembly of molecular complexes directing the secretory pathway principally define the (1) the number of exocytotic sites for release-ready vesicles at the plasma membrane; (2) the relative occupancy of the sites; (3) the probability of stimulus-dependent exocytotic release at each site; and (4) the degree to which renewal processes are engaged to support highly repetitive and/or sustained secretion. In this chapter, we focus on classes of proteins that have been considered "clamps" within the Ca2+-regulated release process.