Within milliseconds of sensing a calcium ion signal, neuronal cells release neurotransmitters into the synaptic junction via primed vesicles docked on the cells’ membranes. The process is essential for information processing in the brain.

The researchers report that a symmetrical arrangement of six proteins appears to enable the coordinated and rapid release of neurotransmitters from their holding pens along the cell membrane.

The authors analyzed images of 7,527 synaptic vesicles at various stages of docking with the membranes of cultured neurons using cryoelectron tomography, which provides 3D visualization at the protein level.

The analysis revealed vesicles are initially tethered 8–18 nm away from the membrane via proteins that do not appear to be arranged in a discernible pattern. Primed vesicles, however, appear to be held within 4 nm of the membrane by a symmetrically arranged complex of six protein masses. Each protein mass connects the synaptic vesicle to the membrane. While resolution prevents identification of the proteins contained within, the authors hypothesize that each mass likely includes a SNAREpin.

According to the authors, these SNAREpins are prearranged into a cooperative fusion machinery structure that forms a critical element of calcium ion signaling.

https://www.pnas.org/content/118/5/e2024029118

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