Cell biology of the synapse

Abstract

Synapses are the sites of contact between nerve cells. Synapses convert electrical signals into chemical information, which is conveyed between neurons at this site. The synapse consists of both pre- and postsynaptic elements. The salient feature of the presynaptic terminal is a cohort of electron-lucent synaptic vesicles, which contain non-peptide neurotransmitters; dense-cored vesicles may also be present and contain catecholamines and neuropeptides. Upon release from the vesicle, these molecules bind to specific receptors on the postsynaptic membrane. The release of the vesicular contents, itself, depends upon an array of proteins present in the vesicular and presynaptic membranes. Among these are the soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs). Beneath the postsynaptic membrane is a dense filamentous array termed the postsynaptic density (PSD). The PSD displays a complex array of proteins, which are arranged in a hierarchical manner: (1) receptors, ion channels, and adhesion proteins shared with the postsynaptic membrane; (2) scaffold proteins connecting the receptors to each other, to other membrane components, and to the actin cytoskeleton; and (3) the actin-based cytoskeleton, itself. A key component of the PSD is the enzyme Ca 2+ /calmodulin-dependent protein kinase II (CaMKII), which is capable of autophosphorylation and, thus, has been implicated in long-term processes. The PSD is important in signal transduction events at the synapse and may be involved in information storage. Receptive surfaces include those on dendrites, dendritic spines, the cell body, and other axon terminals. Dendritic spines contain the cytoskeletal protein actin, which may be involved in spine structural and functional alterations. Some synapses have structural characteristics that are specialized, and these include neuromuscular junctions, ribbon synapses, and squid giant synapses. Whereas all synapses conform to a basic structural plan and transmit information with a great degree of fidelity, synapses also possess the ability to modify the manner in which incoming signals are received, modified, and transmitted, a property termed plasticity. Plasticity depends on the molecular variability present at different synapses and activity-dependent synaptic plasticity, which, in turn, may depend upon local regulation of protein translation.