Synaptic Vesicle

Overview of Synaptic Vesicle in Nervous Systems

Communication in the central and peripheral nervous systems via neurons is mediated by the regulated release of chemical messenger molecules, neurotransmitters. Neurons communicate with other cells through synaptic transmission. The presynaptic nerve terminal is filled with small organelles loaded with a cocktail of physiologically active small molecules. Neurotransmitter release from the presynaptic terminal is triggered by calcium influx. The secreted transmitter molecules induce a physiological response by binding to appropriate receptors. Uptake, storage, and stimulus-dependent release of neurotransmitters are maintained by highly specialized organelles, the synaptic vesicles. These are key organelles in synaptic transmission and many of their numerous tasks are governed by proteins as carriers of function. A detailed characterization of synaptic vesicle-associated proteins will greatly contribute to our further understanding of the molecular mechanisms underlying intercellular communication.

Introduction of Synaptic Vesicles

Synaptic vesicles contain two classes of obligatory components: transport proteins involved in neurotransmitter uptake, and trafficking proteins that participate in synaptic vesicle exo- and endocytosis and recycling. Transport proteins are composed of a vacuolar-type proton pump that generates the electrochemical gradient, which fuels neurotransmitter uptake, and neurotransmitter transporters that mediate the actual uptake. The trafficking proteome of synaptic vesicles is complex. It includes intrinsic membrane proteins, proteins associated via posttranslational lipid modifications, and peripherally bound proteins. These proteins do not share a characteristic that would make them identifiable as synaptic vesicle proteins, and little is known about how these proteins are specifically deposited into synaptic vesicles. Many but not all of the known synaptic vesicle proteins interact with nonvesicular proteins and are linked to specific functions.

Fig.1 Major molecular constituents of cholinergic synaptic vesicles. (Volknandt, 1995)

Synaptic Vesicle Pools

When a nerve terminal is stimulated repeatedly at a high rate, release drops dramatically and eventually reaches a lower steady-state level. The use-dependent initial synaptic depression during high-frequency stimulation reflects the depletion of vesicles in the readily releasable pool. The steady-state level of release corresponds to the rate with which vesicles are replenished into the readily releasable pool by recycling or by recruitment from a reserve pool. The concept of equating release rates with vesicle pools has been useful, and different pools of synaptic vesicles were defined based on the rates of release under various stimulation conditions.

Most synapses rely on three vesicle pools:

Readily releasable pool (RRP): Presynaptic nerve terminals contain a RRP, from which vesicles can be easily mobilized on stimulation;

Reserve pool: Presynaptic nerve terminals contain a large reserve pool, from which vesicles are drawn more slowly, typically in response to intense or prolonged stimulation.

Recycling pool: Recycling pool is released more slowly than the readily releasable pool, and its release precedes reserve pool mobilization.

Table.1 Characteristics of the vesicle pools

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Reference

1. Volknandt, W. The synaptic vesicle and its targets. Neuroscience. 1995, 64(2): 277-300.