Nerve terminal membrane trafficking proteins: from discovery to function

Abstract Release of chemical messengers is the primary means by which neurons communicate with target cells. Chemical neurotransmitters are secreted from the presynaptic nerve terminal, travel across the synaptic cleft, and stimulate receptors on postsynaptic cells in a process termed neurotransmission (1). Initial physiological work demonstrated that neurotransmitter is released in packets or ‘ quanta’, and that each quantum consists of a large number of neurotransmitter molecules (2, 3). Ultrastructural studies indicated that a major feature of the presynaptic nerve terminal is a local concentration of uniformly-sized lipid-bound vesicles, promoting the hypothesis that a quantum of neurotransmitter is stored in a vesicle (4). Subsequently, abundant research demonstrated the primacy of these vesicular structures in neurotransmitter release (5, 6). As each vesicle contains a quantum of neurotransmitter, exquisite control of nervous system communication can result from modulation of the behaviour of synaptic vesicles.