Storage and release of neurotransmitters

Abstract

Because synaptic vesicles and secretory granules are simple in composition and easy to purify, many of their protein components have been identified and often sequenced. Attempts are underway to link the small number of membrane proteins to the small number of functions the vesicles perform. The discovery of sequence homologies has helped greatly with this. In addition, techniques that have begun to prove successful involve microinjection, identification of proteins that bind synaptic vesicle proteins, DNA transfection into cells and oocytes, and more recently, in vitro reconstitution of exocytosis, endocytosis, and vesicle biogenesis. Advances in the latter areas have been strongly influenced by the breakthroughs in our knowledge of membrane traffic in nonneuronal cells. The budding reactions involved in making synaptic vesicles and secretory granules resemble in many ways the generation of carrier vesicles from the ER and the Golgi complex. Finally, exocytosis in neurons may closely resemble fusion of carrier vesicles with target organelles in nonneuronal cells, using complexes of peripheral membrane proteins, GTP hydrolysis, and integral membrane proteins with fusogenic domains. The usefulness of in vitro reconstitution, reverse genetics, and the parallels with better understood systems compensates in part for a major weakness in the field, namely the difficulty in obtaining viable mutants that are defective in the storage and release of secretory vesicle content.