Scientists used X-ray laser technology to uncover never-before-seen details of how the brain sends rapid-fire messages between cells, potentially opening up the door for new drugs to treat brain disorders.
A team of researchers mapped the 3-D atomic structure of a two-part protein complex, SLAC National Accelerator Laboratory reported. Understanding how brain cells release these important signals could help researchers discover new targets for brain disorder drugs.
"This is a very important, exciting advance that may open up possibilities for targeting new drugs to control neurotransmitter release. Many mental disorders, including depression, schizophrenia and anxiety, affect neurotransmitter systems," said Axel Brunger, the study's principal investigator. "Both parts of this protein complex are essential, but until now it was unclear how its two pieces fit and work together."
The two protein parts are called neuronal SNAREs and synaptotagmin-1 and appear as a "helical protein bundle." SNAREs influence the brain's chemical signaling by fusing together packets of neurotransmitters to the outer edges of neurons, allowing them to dock with chemical receptors in another neuron, triggering a response.
The researchers observed that when SNAREs and synaptotagmin-1 combine they amplify calcium concentration, which creates a "gunshot-like" release of neurotransmitters from one neuron to another. The findings also help explain how the proteins fuse together before they reach a neuron's membrane, which sheds light on how the proteins trigger brain signaling so quickly.
"The neuron is not building the 'gun' as it sits there on the membrane - it's already there," Brunger said.
The researchers believe several of the joined protein complexes group together and interact with the same vesicles to trigger neurotransmitter release.
"The new structure has identified unanticipated interfaces between synaptotagmin-1 and the neuronal SNARE complex that change how we think about their interaction by revealing, in atomic detail, exactly where they bind together," said Thomas C. Südhof, a professor at the Stanford School of Medicine and Howard Hughes Medical Institute. "This is a new concept that goes much beyond previous general models of how synaptotagmin-1 functions."
The findings were published in a recent edition of the journal Nature.
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