Neuronal and non-neuronal functions of the synaptic cell adhesion molecule neurexin in Nematostella vectensis

The evolutionary transition from diffusion-mediated cell-cell communication to faster, targeted synaptic signaling in animal nervous systems is still unclear. Genome sequencing analyses have revealed a widespread distribution of synapse-related genes among early-diverging metazoans, but how synaptic machinery evolved remains largely unknown. Here, we examine the function of neurexins (Nrxns), a family of presynaptic cell adhesion molecules with critical roles in bilaterian chemical synapses, using the cnidarian model, Nematostella vectensis. Delta-Nrxns are expressed mainly in neuronal cell clusters that exhibit both peptidergic and classical neurotransmitter signaling. Knockdown of δ-Nrxn reduces spontaneous peristalsis of N. vectensis polyps. Interestingly, gene knockdown and pharmacological studies suggest that δ-Nrxn is involved in glutamate- and glycine-mediated signaling rather than peptidergic signaling. Knockdown of the epithelial α-Nrxn reveals a major role in cell adhesion between ectodermal and endodermal epithelia. Overall, this study provides molecular, functional, and cellular insights into the pre-neural function of Nrxns, as well as key information for understanding how and why they were recruited to the synaptic machinery.