MSc Exit Seminar- Alicia Harracksingh (Senatore lab)

Exploring Protein Interactions between Ca_V2 Calcium Channels and Pre-synaptic Scaffolding Proteins MINT and RIM in Invertebrates

During synaptic transmission, voltage-gated calcium type-2 (Ca_V2) channels mediate transient influxes of Ca²⁺ into the cytoplasm. This event activates synaptic vesicle (SV) calcium sensors, which facilitates docking, priming and fusion at the plasma membrane, and the subsequent release of SV contents into the synaptic cleft. A direct interaction has been proposed to tether Ca_V2 channels and SVs in nanometer proximity, primarily mediated by scaffolding proteins that bind to the distal C-terminus of Ca_V2 at a conserved PDZ-ligand domain. Here, we explored interactions between Ca_V2 and the scaffolding proteins RIM and MINT in vitro in the arthropod Drosophila melanogaster and the cnidarian Nematostella vectensis to understand the evolution of the synapse through conservation of Ca_V2 channel protein structure- function. We found that interactions between these proteins are conserved and occur at similar domains and ligand domains, which suggest that the Ca_V2-MINT and Ca_V2-RIM interactions serve as important evolutionary adaptations for the emergence of synapses.