Thanks to a protein that helps fruit flies remain airborne, researchers have deciphered a key step in synapse maturation. Fouquet et al. show that the protein forms part of a synaptic structure that clusters the calcium channels necessary for neurotransmitter release.
The active zone of the presynaptic terminal lives up to its name. Vesicles crowd in to discharge their loads of neurotransmitter into the synaptic cleft. Bunches of calcium channels swing open when an action potential arrives and then shut. Also located at the active zone are filaments that extend into the cytoplasm. At the neuromuscular junction of fruit flies, these structures, known as T-bars disappear when the active zone protein Bruchpilot is missing. Calcium channels also disperse. Researchers thought that Bruchpilot, German for “crash pilot,” a reference to the aerial ineptitude of insects lacking the protein, helps corral calcium channels and thus boosts synaptic efficiency. But whether Bruchpilot was a signaling protein or a structural component of T-bars was unclear.
By studying the effects of different Bruchpilot mutants on synapse development, Fouquet et al. showed that the protein is a building block for T-bars. Bruchpilot seems to stretch out along the T-bar, with its N-terminal close to the calcium channels of the active zone membrane. The team found that Bruchpilot moves into the active zone fairly late in development of an individual synapse, slightly after one component of the calcium channels. Although Bruchpilot can latch onto this component, the asynchrony suggests that the protein doesn't help tow the channels to the active zone. Instead, Bruchpilot's job might be to help them remain gathered there. The next question to answer, the researchers say, is how T-bars affect the movement of vesicles to the active zone membrane.