C. elegans MAGU-2/Mpp5 homolog regulates epidermal phagocytosis and synapse density.

Synapses are dynamic connections that underlie essential functions of the nervous system. The addition, removal, and maintenance of synapses govern the flow of information in neural circuits throughout the lifetime of an animal. While extensive studies have elucidated many intrinsic mechanisms that neurons employ to modulate their connections, increasing evidence supports the roles of non-neuronal cells, such as glia, in synapse maintenance and circuit function. We previously showed that C. elegans epidermis regulates synapses through ZIG-10, a cell-adhesion protein of the immunoglobulin domain superfamily. Here we identified a member of the Pals1/MPP5 family, MAGU-2, that functions in the epidermis to modulate phagocytosis and the number of synapses by regulating ZIG-10 localization. Furthermore, we used light and electron microscopy to show that this epidermal mechanism removes neuronal membranes from the neuromuscular junction, dependent on the conserved phagocytic receptor CED-1. Together, our study shows that C. elegans epidermis constrains synaptic connectivity, in a manner similar to astrocytes and microglia in mammals, allowing optimized output of neural circuits.