The trans-synaptic nanocolumn

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This video portrays our new model of the molecular architecture at points of neuron-to-neuron contact in the brain, based on measuring the location of individual protein molecules at the sites where cell contact is made. Amazingly, proteins in the two cells align with each other to extremely high accuracy, suggesting a protein column spanning the two cells, and assuring that neurotransmitter release occurs with highest probability near the receptors that sense it.

This finding strengthens our understanding of the synapse, a truly fundamental component of the brain’s circuitry. Moreover, because many proteins at the synapse and in the nanocolumn are linked to psychiatric and neurological disorders ranging from schizophrenia and autism to intellectual disability and addiction, this new understanding offers many new ideas about the cellular basis of many of our greatest health-care challenges.

In the video, the measured localization’s of RIM1/2 and PSD-95 at one synapse are taken as the starting point for illustrating nanocolumn organization in context. The model is to scale, and protein features are derived from crystal structures where possible. Cell structure and the position of vesicles and other molecules are hypothetical. The green columnar guides indicate where the peaks of protein gradients align across the cleft, as deduced using methods from the paper.

[Source: Tom Blanpied YouTube link]