Miller, AdamLasseigne, Abagael2021-09-132021-09-132021-09-13https://hdl.handle.net/1794/26632Electrical synapses are specialized cellular adhesions that allow for the direct flow of information between neurons. They are required for proper neural circuit development and make up an estimated 20% of synapses in adult nervous systems. Despite this, we know very little about their molecular structure. We often consider them to simply be aggregates of Connexin protein channels, and, up until now, it has been unclear whether electrical synapses require other support proteins for them to form and function. In this thesis, I show that not only do electrical synapses require the support of another molecule, but their formation is actually dictated by it. A comparison of electrical synapses to other cellular adhesions led me to hypothesize that they would require an intracellular scaffolding molecule to instruct their formation. Using forward and reverse genetics, the scaffolding protein Zonula occludens-1 (ZO1) was identified as being critical for Connexin protein localization to the electrical synapse. Further, I showed that its organizational role at the synapse is mediated by a direct interaction with the postsynaptic Connexin. The presence and requirement of ZO1 at the electrical synapse forces us to update our simple model and shows that electrical synapses are complex structures that require molecular organization beyond the channel-forming Connexin proteins. This dissertation contains previously published and co-authored material.en-USAll Rights Reserved.cell biologyconnexinelectrical synapseMAGUK scaffoldsynaptogenesisZO1Electronic Thesis or Dissertation