Scientists at The Hospital for Sick Children have used advanced imaging technology to uncover the atomic structure of an enzyme that neurons use to communicate. Communication between neurons through synapses is crucial for all brain activity, including memory, emotion, learning, and motor control. The research team, led by Dr. John Rubinstein, hopes that by understanding how chemicals are released from neurons, they may be able to identify new therapeutic targets for conditions such as epilepsy.
Neurons release neurotransmitters into synapses to communicate with other neurons, and an enzyme called vesicular-type ATPase (V-ATPase) helps facilitate this process. The V-ATPase acts as a pump to drive neurotransmitters into synaptic vesicles and regulates neurotransmitter release. The research team found that the V-ATPase controls neurotransmitter release by spontaneously falling apart after the vesicles are loaded with neurotransmitters, which allows for the release of the neurotransmitters.
To capture images of this process, the researchers used novel biochemical and imaging methods supported by the SickKids Nanoscale Biomedical Imaging Facility. By isolating synaptic vesicles and using cryogenic electron microscopy to image them at high resolution, the team was able to create 3D models of the V-ATPase. They discovered that the V-ATPase interacts with various components of the synaptic vesicle, including a protein called synaptophysin, which could be helping to recruit V-ATPase to synaptic vesicles.
Moving forward, the researchers plan to investigate the role of the interaction between V-ATPase and synaptophysin in synaptic vesicles with the aim of understanding how this process controls the release of neurotransmitters. This research could potentially lead to the development of new therapeutic targets for various health conditions, including epilepsy. The study was funded by the Canadian Institutes of Health Research, the University of Toronto, and the Natural Sciences and Engineering Research Council, with support from the Canada Foundation for Innovation and the Ontario Research Fund.
By uncovering the atomic structure of an enzyme crucial for neuronal communication, the researchers have provided new insights into how neurotransmitters are released from synaptic vesicles. This discovery could have significant implications for improving care for children with epilepsy and other neurological conditions. The use of advanced imaging technology has allowed for a clearer understanding of synaptic function, which may inform the development of new therapeutic approaches.
Overall, this research highlights the importance of understanding the intricate processes involved in neuronal communication and neurotransmitter release. By identifying key interactions between proteins within synaptic vesicles, the researchers have opened up new possibilities for targeting these processes in the treatment of various health conditions. The findings of this study have the potential to pave the way for future advancements in the field of neuroscience and the development of novel therapeutic interventions.