Research led by York University investigated the role of protein transport to fine-tune communications between neurons. Understanding how communication between nerve cells is built, maintained and protected over a lifetime is one of the most important questions in the neurosciences.
Under the supervision of Professor Georg Zoidl, graduate student Cherie Brown undertook this ground-breaking research, the findings of which were published in the journal Cells (September, 2019).
Zoidl, who is in both the Faculties of Health and Science, is the Canada Research Chair for Molecular and Cellular Neuroscience. He is also an associate member of Vision: Science to Applications (VISTA) and a member of the Centre for Vision Research. His research program aims to clarify how cells of the eye and the brain communicate through specialized cell junctions and how changes in this process can lead to impairment of vision, learning and memory.
The research team included scientists from Albert Einstein College (New York) and the Federal University of Rio de Janeiro (Brazil). This study was funded by the Natural Sciences and Engineering Research Council and the National Institutes of Health (US).
Brown and Zoidl sat down with Brainstorm to discuss this article and the importance of this work.
Q: Please describe for our readers the chief goals of your work.
CB: My work addresses fundamental cell biology, more specifically neurobiology. We are trying to understand how cells communicate. We’re looking deeper into a process called plasticity, which means that the neurons can regulate or control how they communicate with each other.
Q: What were the objectives of this recent study published in Cells?
CB: We were trying to fill a major knowledge gap about the mechanisms of neuronal communication. To close this gap, we have been looking at important steps in the life cycle of a critical protein. Specifically, we have filled the time it spends between two bookends, that is after it is born and before it is helping to exchange information between nerve cells. This is where transport comes into play. My major goal is looking at how this protein is transported to influence plasticity.
Q: What is the role of protein?
CB: The protein I am studying is connexin-36. What it does is form a tube or tunnel, called a gap junction channel, between two cells. The channel allows for the neurons to communicate with each other by letting small molecules easily pass through.
Q: How did you go about the study?
CB: We used cutting-edge imaging technology. Essentially, I tagged my protein connexin-36 with a fluorescent probe for visualization. We used high-power microscopy techniques to look at where the protein is in the cell and where it’s going.
GZ: Microscopy allows us to track the proteins. Because they are fluorescent, they will look like little dots on a cell. We can track where they start their life and where they end their life; over time, you can really resolve everything from birth to death of these proteins.
Q: What were your key findings?
CB: We found that connexin-36 interacts with what’s known as microtubules – a major transport highway of cells. We determined where microtubules bind on the connexin 36 protein, and that this interaction is influencing the ability of neurons to communicate with each other. Essentially, when we have less connexin-36 protein transported to its endpoint to form the gap junction channel, we know that means less communication is possible. More protein transported leads to more communication between paired neurons.
Q: Did anything surprise you about this finding?
CB: Yes, we found out that the specific region where microtubules and connexin 36 interact with each other is very fragile. Manipulating that binding region will nearly eliminate the interaction between these two proteins and as a consequence, connexin 36 won’t transport properly. Even just a small change in this binding region is very detrimental to the overall function of connexin-36 in the cell.
Q: What kind of an impact will this new knowledge have?
CB: We are performing fundamental neurobiology, with the hopes of updating what we know about neuron communication. This is significant when we think of higher order processes of the nervous system, like vision. We are trying to explain this on a cellular level.
Q: How could this research be applied? Is there a disease or condition that this research could help?
CB: When you think of neurodegeneration, anything that affects communication between neurons, this research could play a role. I like to use the examples of Alzheimer’s or Parkinson’s diseases.
Q: How has York supported your research?
GZ: Look at the building [Life Sciences]. York University is providing the platform, the infrastructure to perform cutting-edge, fundamental neurobiology.
Q: York values its graduate students. They play a key role at the University. Could you tell us about your PhD student Cherie Brown?
GZ: Cherie is one of our stars. She is a perfect example of women in STEM. She has been invited to speak at international conferences and has received two major awards in the last two years. The most recent was the IGJC Star Award this year. She is almost finished her PhD and already got job offers.
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By Megan Mueller, senior manager, Research Communications, Office of the Vice-President Research & Innovation, York University, firstname.lastname@example.org