Cell Biology

Orchestrating Post-and-Beam Construction

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Science  23 Feb 2001:
Vol. 291, Issue 5508, pp. 1451
DOI: 10.1126/science.291.5508.1451b

Assembly of the presynaptic active zone in neurons is a crucial step in the formation of the chemical synapse. Within this region are calcium channels, protein aggregates (active zone material or AZM), and synaptic vesicles with their neurotransmitter cargoes.

Although many of the molecular components of the active zone have been identified, Harlow et al. have now performed a three-dimensional reconstruction of the AZM of the frog neuromuscular junction. With an array of interconnected pegs, ribs, and beams, the AZM appears to be a scaffold that juxtaposes the synaptic vesicles and calcium channels. At right angles to the centralized beams, the ribs appear to position synaptic vesicles for docking and fusion, and the pegs (to which the ribs are attached) seem to bind to (or may be) the intracellular domains of the presynaptic calcium channels.

To address the question of how active zone components are assembled, Zhai et al. have investigated developing synapses of rat hippocampal neurons. The structural proteins Piccolo and Bassoon, along with syntaxin, SNAP-25, and N-cadherin, all arrive at the presynaptic staging ground in large (80 nanometer) granulated vesicles. Deciphering how these proteins relate to the pegs, ribs, and beams will be next. — OMS

Nature409, 479 (2001); Neuron29, 131 (2001).

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