Researchers close knowledge gap on the ‘plasticity’ of brain cell connections

Graduate students from the labs of Professors Georg Zoidl, Canada Research Chair Tier I in Biology & Psychology, and Logan Donaldson in the Faculty of Science have made important new gains in understanding how brain cells communicate with each other through specialized contact sites called electrical synapses.

photo of the zoidl-donaldson research team

From left, the research team members, Ekaterina Smirnova, Georg Zoidl, Christiane Zoidl, Logan Donaldson, Ryan Siu and Cherie Brown

At an electrical synapse, two brain cells are linked together by a “gap junction”, which contains channels that conduct nerve impulses. Researchers already know that synapses can adapt to become stronger or weaker – called “plasticity”, which is important for memory and learning – and that there are certain proteins that help with this. For instance, previous research has already shown that a protein called connexin36 (Cx36) interacts with an enzyme called calcium/calmodulin-dependent kinase II (CaMKII) to initiate plasticity. Until now, however, the details of this interaction have remained unclear.

“Connexin proteins are the conduit in which electrical signals are passed between neurons and then multiplied vastly by the number of connections between the cells,” says PhD student Ryan Siu, who led the research. “Using sophisticated imaging techniques, I was able to spy on this process in living cells at a distance of less than 10 nanometres, which is comparable to the distance of only 100 atoms laid end-to-end.”

artist's rendering of Calmodulin interaction complex with Connexin36 protein

Calmodulin interaction complex with Connexin36

In their study, Siu and his team combined a number of high-resolution imaging techniques available at the Life Sciences Building at York University to determine that Cx36 first binds to another protein called calmodulin (CaM). They identified how the two proteins bind at the atomic level and found that this interaction is a critical step before Cx36 interacts with CaMKII. Their findings were published in the journal Frontiers in Molecular Neuroscience.

“This interdisciplinary study exposed me to a combination of advanced microscopy techniques used at the forefront of molecular and cellular neuroscience, as well as biophysical techniques that provided me a way to determine how calmodulin interacts with connexin at an atomic level of detail,” says PhD student Ekaterina Smirnova. “This experience in the York University graduate program demonstrates the power of approaching scientific questions from many different perspectives.”

The research findings will help scientists understand how brain cells adapt to different kinds and levels of signals. Zoidl notes that “by studying the proteins that play a role in communication processes, we will better learn about the molecular and cellular basis of cognitive processes and how brain disorders might arise when they are compromised.”

This research builds upon an initial discovery by his group published in the prestigious journal PNAS (DOI: 10.1073/pnas.0805408105), and it is the second cell signaling paper published in 2016 in collaboration with Donaldson’s lab.

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