by Aaron Gochman (’18)

Intercellular communication in the central nervous system occurs at a synapse, the gap between two neurons. The presynaptic neuron releases a chemical messenger known as a neurotransmitter, which diffuses across the synapse and relays the signal to the postsynaptic cell.

The process of releasing the neurotransmitter from the presynaptic cell is quite complicated. The mechanism includes packing the neurotransmitter inside a vesicle, docking the vesicle in the membrane, and fusing the vesicle with the membrane to release its contents. The most critical phase in this process, fusing the vesicle with the membrane, involves complexin, an important modulatory protein that regulates release of the vesicle in the presence of calcium ions.

A team of researchers from Stanford University has offered a clue about the mechanism by which complexin regulates the spontaneous release of the vesicle so that it fuses with the membrane. Complexin can be bound in either the cis or trans conformations, both of which were studied in the experiments conducted by the researchers; the results showed that the different conformations caused markedly different phenotypes. Whereas in the cis conformation neurotransmitter release involved more steps, the trans conformation release allowed for a smoother process. This difference is important because it aids our understanding of which conformation is involved in which type of release.

References:

1. U. Choi, et. al., Complexin induces a conformational change at the membrane-proximal C-terminal end of the SNARE complex. eLife 5, (2016), doi: http://dx.doi.org/10.7554/eLife.16886.
2. K.R. Weninger, Complexin Arrests a Neighbor. Nature Structural & Molecular Biology 18.8, (2011).