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Asymmetry of an intracellular scaffold at vertebrate electrical synapses

Audrey J Marsh, Jennifer Carlisle Michel, Anisha P Adke, Emily L Heckman, Adam C Miller
doi: https://doi.org/10.1101/173955
Audrey J Marsh
Institute of Neuroscience, Department of Biology, University of Oregon, Eugene, OR, USA.
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Jennifer Carlisle Michel
Institute of Neuroscience, Department of Biology, University of Oregon, Eugene, OR, USA.
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Anisha P Adke
Institute of Neuroscience, Department of Biology, University of Oregon, Eugene, OR, USA.
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Emily L Heckman
Institute of Neuroscience, Department of Biology, University of Oregon, Eugene, OR, USA.
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Adam C Miller
Institute of Neuroscience, Department of Biology, University of Oregon, Eugene, OR, USA.
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  • For correspondence: acmiller@uoregon.edu
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Abstract

Neuronal synaptic connections are electrical or chemical and together are essential to dynamically defining neural circuit function. While chemical synapses are well known for their biochemical complexity, electrical synapses are often viewed as comprised solely of neuronal gap junction channels that allow direct ionic and metabolic communication. However, associated with the gap junction channels are structures observed by electron microscopy called the Electrical Synapse Density (ESD). The ESD has been suggested to be critical for the formation and function of the electrical synapse, yet the biochemical makeup of these structures is poorly understood. Here we find that electrical synapse formation in vivo requires an intracellular scaffold called Tight Junction Protein 1b (Tjp1b). Tjp1b is localized to electrical synapses where it is required for the stabilization of the gap junction channels and for electrical synapse function. Strikingly, we find that Tjp1b protein localizes and functions asymmetrically, exclusively on the postsynaptic side of the synapse. Our findings support a novel model in which there is molecular asymmetry at the level of the intracellular scaffold that is required for building the electrical synapse. ESD molecular asymmetries may be a fundamental motif of all nervous systems and could support functional asymmetry at the electrical synapse.

Footnotes

  • Support: Funding was provided by the National Institute of Neurological Disease and Stroke R00NS085035 and startup funds from the University of Oregon to A.C.M.

  • We declare that we have no competing interests.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted August 09, 2017.
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Asymmetry of an intracellular scaffold at vertebrate electrical synapses
Audrey J Marsh, Jennifer Carlisle Michel, Anisha P Adke, Emily L Heckman, Adam C Miller
bioRxiv 173955; doi: https://doi.org/10.1101/173955
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Asymmetry of an intracellular scaffold at vertebrate electrical synapses
Audrey J Marsh, Jennifer Carlisle Michel, Anisha P Adke, Emily L Heckman, Adam C Miller
bioRxiv 173955; doi: https://doi.org/10.1101/173955

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