As people begin reading this sentence, vesicles, or packages within cells transporting cargo-like neurotransmitters, are being released instantly and rapidly over a chain of nerves connecting their eyes to their brain, helping them view and process the words on the page.
Almost 45 years after neurotransmitters and the way they are released was discovered, researchers at the University of Wisconsin uncovered a key component in the mechanism by which neurons in the brain communicate.
The research team consisted of professor Edwin Chapman and Hua Bai, a research assistant, both from School of Medicine and Public Health, and Huisheng Liu, a research assistant from the UW Waisman Center. Their findings were published last month, a statement from the department said.
The team found that a specific protein may be a controlling factor in the process of indicating when and how vesicles are released, Liu said.
When activated by a calcium ion, Liu said a protein known as synaptotagmin, or ‘syt’, is responsible for enabling large amounts of synaptic vesicles in nerve cells to be released in a matter of milliseconds, thereby allowing for coordination of body movement.
The newfound step involves the syt protein physically penetrating the target cell membrane, Chapman said. The physical interaction is what enables quick transmission between neurons, he said.
“We have known that [the calcium ion] triggers neurotransmitter release for many decades, but we did not know how this occurs,” Chapman said. “The study uncovered a key step in the process of neurotransmitter release.”
The study is the first time direct physiological evidence was provided to demonstrate that penetration of syt into the plasma membrane manipulates the fast and robust synaptic release, Liu said.
It was primarily concerned with how the syt protein regulates this fast and robust synaptic vesicle release, he said.
“My colleagues and I hypothesized that the regulation of syt on fast release may need interaction between its two conservative domains, C2A and C2B,” Liu said.
To test this hypothesis, the research team altered several aspects of the two conservative domains, including their distance apart and flexibility, he said.
Using these techniques, the research team was able to determine the way syt protein regulates vesicle-membrane fusion involves physical penetration into the target membrane, Liu said.
“Our findings provide a model in which syt acts, at least in part, by ‘dipping’ into the target membrane,” he said. “This drives local bending and accelerating of the fusion of synaptic vesicles with the plasma membrane.”
The study of neurotransmission with synaptic vesicles is something that has been explored in depth, Chapman said. He and his colleagues have published more than 100 papers on the topics related to exocytosis and endocytosis, the processes of vesicle creation and fusion, he said.
UW’s reputation in scientific research benefited the team’s ability to acquire research funding from the government and private groups, Liu said. Its many interdisciplinary research teams also helped the research team to rethink their studies in full perspective, he said.
“UW has comprehensive facilities and resources so that experiments using different technologies can be carried out quickly,” Liu said. “I can always have latest knowledge about the study of neurotransmission.”
