The classic image of communication between brain cells shows a neurotransmitter crossing the synapse and binding to receptors on the surface of a neighboring neuron. Yet, scientists have had only a murky picture of the events within the secreting neuron that trigger the release of neurotransmitters.
Now, a group of researchers led by Axel T. Brunger, a Howard Hughes Medical Institute (HHMI) investigator at Yale University has deciphered and produced the first glimpses of the molecular machinery that propels neurotransmitters into the synapse. The key players are a family of proteins called SNAREs (Soluble NSF Attachment protein REceptor). These proteins haven't changed much through evolution; SNAREs play a similar role in the secretions of even primitive life forms like yeast.
In neurons, the merging of these mostly amorphous proteins into a highly structured and charged complex precipitates neurotransmitter release. Formation of the complex fuses vesicles -- tiny sacs carrying the neurotransmitter inside the neuron -- with the cell membrane, spewing the neurotransmitter into the synapse. Such vesicle fusion occurs millions of times daily in each of the human brain's 100 billion neurons. So understanding vesicle fusion promises to shed light on processes like learning and memory, and may lead to improved treatments for brain disorders.
"It's sort of like merging two soap bubbles into one, but hardly that simple," explained R. Bryan Sutton, an HHMI associate in Brunger's laboratory. Sutton, Brunger and their colleagues report the elucidation of the synaptic fusion complex's intricate molecular structure in the September 24, 1998, issue of Nature.
The researchers used ultra-bright x-ray radiation from a synchrotron facility
funded by the U.S. Department of Energy to illuminate the tiny protein crystals
and determine the shape of the complex, atom-by-atom. They then created computer
reconstructions that provide clues about how this pivotal protein comp
'"/>
Contact: Jim Keeley
keeleyj@hhmi.org
(301) 215-8858
Howard Hughes Medical Institute
23-Sep-1998