Presynaptic active zones are the specialized sites from which nerves release neurotransmitter. They are characterized by the presence of calcium channels, synaptic vesicles containing neurotransmitter, and aggregates of protein that make up what is known as 'active-zone material'. This material was described by S. L. Palay almost 50 years ago (J. Biophys. Biochem. Cytol. 2, 193–202; 1956), but its precise structure and function have remained an enigma. Things may be about to change, however, thanks to the publication elsewhere in this issue of stunning three-dimensional reconstructions of the frog neuromuscular junction (Nature 409, 479–484; 2001).
To study this junction between nerve and muscle, M. L. Harlow and colleagues used a technique known as electron microscope tomography, which gives greater spatial resolution than conventional transmission electron microscopy. They describe three distinct elongate structures — which they call ribs, beams and pegs — that make up the first 15 nanometres of active-zone material as one looks into the neuron. The top image shows this view, with the active-zone material in yellow and the synaptic vesicles in blue.
Beams — which make up the vertical band in the centre of this image — are arranged along the long axis of the elongate active zone, and form the backbone of the structure. Ribs lie perpendicular to this long axis, and link the central backbone to the double row of synaptic vesicles that straddle it. Pegs (not apparent in these images) tether each rib to the plasma membrane in a pattern that matches the distribution of molecules that are thought to be calcium channels. The lower image is a side-on view, with the presynaptic plasma membrane in grey. The structure is perhaps best appreciated in the movies published on Nature's web site (http://www.nature.com/nature/).
As a whole, the active-zone material appears to provide a scaffold by which synaptic vesicles are localized to the specialized presynaptic membrane. But the proteins that make up the structure probably have more specific functions. The intracellular domains of calcium channels may form all or part of the pegs, and ribs may be composed of the host of proteins that together mediate docking and fusion of vesicles with the presynaptic membrane. We eagerly await the formal identification of the rib, beam and peg proteins.