Scientists at The Hospital for Sick Children (SickKids) have utilized advanced imaging technology to uncover the atomic structure of an enzyme essential for neuronal communication for the first time.
All brain functions, including memory, emotion, learning, and motor control, rely on communication between neurons through synapses. Neurons release chemical signals known as neurotransmitters across synapses to communicate with other cells. The brain boasts around 100 trillion synapse connections between neurons.
A recent study published in Science demonstrates models based on hundreds of thousands of high-resolution images that provide new insights into synaptic function.
Dr. John Rubinstein and Dr. Claire Coupland led the research team at the SickKids Nanoscale Biomedical Imaging Facility. Their goal is to utilize imaging and modeling techniques to identify potential therapeutic targets for enhancing care for children with epilepsy and other neurological disorders.
Key Findings on Neuronal Communication:
Neurons release neurotransmitters into synapses through synaptic vesicles, which are then reabsorbed and repackaged for subsequent signaling. The enzyme V-ATPase plays a crucial role in this process by facilitating neurotransmitter movement and regulating release from vesicles.
Imaging the Communication Process:
The team used innovative biochemical and imaging methods at the facility to capture high-resolution images of synaptic vesicles and analyze the role of V-ATPase within them. Cryogenic electron microscopy was employed to create 3D models that revealed the interaction of V-ATPase with various synaptic vesicle components.
Surprisingly, the study uncovered an interaction between V-ATPase and synaptophysin, a protein previously not well understood. This interaction sheds light on how synaptophysin aids in recruiting V-ATPase to synaptic vesicles during their formation.
Future Directions:
The team aims to further investigate the V-ATPase and synaptophysin interaction in synaptic vesicles and its impact on neurotransmitter release. Understanding this process could pave the way for potential therapeutic interventions in conditions such as epilepsy.
Funding for this research was provided by the Canadian Institutes of Health Research (CIHR), University of Toronto, Natural Sciences and Engineering Research Council (NSERC), Canada Foundation for Innovation, and Ontario Research Fund.
