Matkovic et al. describe how a protein matrix may position synaptic vesicles close to the calcium signals that trigger their release.
Synaptic vesicles are released at the active zones of presynaptic membranes where voltage-gated calcium channels are clustered together by a dense matrix of cytoplasmic scaffold proteins. In Drosophila, these active zone matrices are known as T bars, and their assembly relies on an elongated protein called Bruchpilot (BRP). In the complete absence of BRP and T-bar assembly, calcium channels are dispersed and vesicle release and synaptic transmission are impaired, but BRP’s precise function is unclear.
Matkovic et al. found that flies express two isoforms of BRP. Each isoform formed separate clusters that alternated in a circular array to form the T bars of Drosophila neuromuscular junctions. In contrast to BRP-null flies, Drosophila lacking only one of the isoforms still formed T bars that clustered calcium channels in the presynaptic membrane. These T bars were smaller, however, and synaptic transmission was still impaired because neurons contained a smaller pool of readily releasable vesicles. Accordingly, the researchers saw fewer synaptic vesicles docked near calcium channels at the base of T bars lacking one BRP isoform.
Senior author Stephan Sigrist thinks the alternating arrangement of BRP isoforms helps assemble T bars with a specific number of “release slots” where synaptic vesicles can be coupled to calcium channel activity. Because BRP’s distal C terminus can capture synaptic vesicles far from the plasma membrane, Sigrist speculates the protein might transfer these vesicles into their membrane-proximal release slots.
Text by Ben Short