Scientists in the Multiscale Bioimaging Cluster of Excellence have succeeded for the first time in simultaneously displaying the motion profiles of a large number of proteins in the synapse. Published in The EMBO Journal.
The contact sites between nerve cells, the synapses, have been extensively studied over the last decades, extending our understanding of brain functioning on a molecular level. Regarding the identity, numbers, and positions of protein molecules present in the synapses a very detailed view already exists. In contrast, very limited information is available about the dynamics and mobility of these proteins in living synapses.
Snapshot of protein mobility in the synapse.
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Knowledge of the mobility rates of the key synaptic proteins would help to understand how these proteins are involved in synaptic signal transduction, and what the possible mechanisms are that regulate their distribution in the synapses.
A team of scientists around Prof. Silvio O. Rizzoli, Director of the Institute of Neuro- and Sensory Physiology of the University Medical Center Göttingen (UMG), and speaker of the Board of the Center for Biostructural Imaging of Neurodegeneration (BIN), and Prof. Sarah Köster, Institute for X-Ray Physics at the Georg-August-University Göttingen, was able to generate the first visualizations of movement of 45 proteins in a cell simultaneously, thus demonstrating the realistic mobility of thousands of protein molecules represented in their realistic shapes and sizes within a synapse.
"Our entire data set can be exploited worldwide by laboratories specialized in neuronal and synaptic modeling for generation of multi-reaction models of the synapse", says Rizzoli, Director of the Institute of Neuro- and Sensory Physiology and senior author of the study. "The use of such datasets will reveal important details about synaptic activity in health and neurological or neurodegenerative diseases", explains Rizzoli. These visualizations can also be appreciated by the general public, and might become a useful educational tool to demonstrate the complexity and dynamics of the cells at the nanoscale.
While mobility of a few individual proteins was assessed in the past, it remains challenging to measure mobility of multiple different proteins in a complex environment as a living synapse. The aim of the present study was therefore to obtain a comparative data set on the mobility of up to 50 different proteins in synapses and axons of living neurons in a brain region (hippocampus) involved in memory formation. "We aimed to understand how protein distribution and mobility in the synapses is regulated, and what the contribution of the synaptic vesicle cluster is, as well as to analyze the connections between protein mobility and various functional protein parameters", explains Sofiia Reshetniak, PhD student at the Institute of Neuro- and Sensory Physiology and first author of the study.
By combining fluorescence recovery after photobleaching, particle tracking, electron microscopy, and in silico modelling, the mobility of 45 different proteins in living neurons has been analyzed and their movement speeds in the form of diffusion coefficients in synapses and axons has been obtained. "Interestingly, the protein size has only a very limited effect on the mobility of proteins", says Prof. Köster, one of the senior authors of the study. "Instead, protein association with the synaptic vesicle cluster plays a much more important role", Köster adds.