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

Abstract

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.

Keywords:

• MAGUK
• synapse elimination
• glia
• miniSOG
• neuromuscular junction
• ACR-2

Acknowledgements

We thank the members of the Jin laboratory for constructive comments. We thank J.S. Dittman for reporter lines. We appreciate Wormbase for genetic and genomic information.

Author contributions

S.J. Cherra and Y. Jin conceived and designed the experiments, interpreted results, and wrote the manuscript. S.J. Cherra also performed experiments and analyzed data. A. Goncharov performed electron microscopy experiments and analyzed data. D. Boassa and M. Ellisman helped develop miniSOG stimulation and detection protocol.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

Some strains were provided by National BioResource Project (Dr. S. Mitani) and the Caenorhabditis Genetics Center, which is funded by the National Institutes of Health Office of Research Infrastructure Programs [P40-OD010440]. The electron micrographs were taken in the UCSD Cellular and Molecular Medicine Electron microscopy core facility, which is supported in part by National Institutes of Health Award [S10-OD023527]. This work was supported by grants from the National Institutes of Health to S.J.C. [K99-NS097638], D.B. [R01-GM086197], M.E. [P41-GM103412], and Y.J. [R01 and R37-NS035546].