Phosphoproteins and the Regulation of Vesicular Neurotransmitter Release

Neurotransmission requires rapid docking, fusion and recycling of neurotransmitter vesicles in the nerve terminal. Many of the proteins involved in this complex mechanism have now been identified (reviewed by Scheller, 1995; Sudhof, 1995) and are present in presynaptic nerve terminals, where they constitute the molecular apparatus for the storage and secretion of neurotransmitters and termination of their effects. Presynaptic nerve terminals store a variety of different neurotransmitters in vesicles which are secreted into the extracellular space by means of regulated exocytosis i.e. upon a specific signal, usually a depolarization-induced Ca2+ influx. Neurotransmitter-containing vesicles firmly dock at the presynaptic plasma membrane prior to exocytosis and are rapidly reclaimed and recycled after fusion and secretion. In mammalian brain nerve terminals two classes of secretory neurotransmitter vesicles can be distinguished on an ultrastructural basis, namely small clear-cored vesicles and large dense-cored vesicles (reviewed by Kelly, 1993). Small clear-cored vesicles, which store neurotransmitters such as glutamate, GABA, glycine, acetylcholine and possibly catecholamines, are released swiftly at the active synaptic zone and undergo multiple cycles of exo- and endocytosis within the nerve terminal. Large dense-cored vesicles, which contain catecholamines or a variety of neuropeptides, on the other hand, cannot refill after exocytosis and therefore need to be recycled via the trans Golgi network.