The Role of Synaptic Adhesion Molecules in Electrical Synapse Formation in Zebrafish

Presenter: Margaret Grivette − Neuroscience

Faculty Mentor(s): Adam Miller, Jen Michel

Session: (In-Person) Poster Presentation

Chemical and electrical synapses work together to shape brain function but little is known about the regulation of electrical synapse formation4. Chemical synapses are junctions that send neurotransmitters across the gap to the receiving neuron. Electrical synapses are physically connected by connexin proteins which are supported by scaffolding proteins that allow charged ions to diffuse between neural cells1. ZO1b is a MAGUK scaffolding protein required for the formation and function of electrical synapses. It contains three PDZ binding domains that bring other proteins together to organize multiple interactions 1,2. Kirrel proteins belong to the transmembrane immunoglobulin superfamily of cell adhesion proteins and have a cytoplasmic PDZ binding domain (PBD). Kirrel 3 is particularly important because alterations in the gene are associated with intellectual disability and the Kirrel 3 protein has recently been found to help build synapses in the mouse hippocampus 3. To determine whether Kirrels may play a role in electrical synapse formation in zebrafish, we tested whether the predicted Kirrel 3 PDB binds to ZO1b PDZ domains using an in vitro binding assay. We found that the Kirrel 3 C-terminus binds to PDZ1 of ZO1b. This interaction is dependent upon the predicted PDB since removal of the last 6 amino acids of the Kirrel 3 tail abolished the interaction.

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