A Two-Immunoglobulin-Domain Transmembrane Protein Mediates an Epidermal-Neuronal Interaction to Maintain Synapse Density

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23 Scopus citations


Synaptic maintenance is essential for neural circuit function. In the C. elegans locomotor circuit, motor neurons are in direct contact with the epidermis. Here, we reveal a novel epidermal-neuronal interaction mediated by a two-immunoglobulin domain transmembrane protein, ZIG-10, that is necessary for maintaining cholinergic synapse density. ZIG-10 is localized at the cell surface of epidermis and cholinergic motor neurons, with high levels at areas adjacent to synapses. Loss of zig-10 increases the number of cholinergic excitatory synapses and exacerbates convulsion behavior in a seizure model. Mis-expression of zig-10 in GABAergic inhibitory neurons reduces GABAergic synapse number, dependent on the presence of ZIG-10 in the epidermis. Furthermore, ZIG-10 interacts with the tyrosine kinase SRC-2 to regulate the phagocytic activity of the epidermis to restrict cholinergic synapse number. Our studies demonstrate the highly specific roles of non-neuronal cells in modulating neural circuit function, through neuron-type-specific maintenance of synapse density. Maintenance of synapses is required for robust circuit function during the lifetime of an animal. Cherra and Jin have identified a novel two-Ig-domain transmembrane protein that mediates the interaction between neurons and epidermis to maintain synapse density through phagocytosis in C. elegans.

Original languageEnglish
Pages (from-to)325-336
Number of pages12
Issue number2
StatePublished - 2016

Bibliographical note

Funding Information:
We thank J.-L. Bessereau, J.S. Dittman, E.M. Jorgensen, J.M. Kaplan, Y. Kohara, A.V. Maricq, K. Shen, and Z. Zhou for strains and reagents. We acknowledge A. Goncharov for electron microscopy. We are grateful to A.D. Chisholm and our lab members for advice and comments. Some strains were provided by S. Mitani and the Caenorhabditis Genetics Center, which is funded by NIH Office of Research Infrastructure Programs (P40 OD010440). This work was supported by NIH grants (NS035546 to Y.J. and F32 NS081945 to S.J.C. and T32 NS7220). Y.J. is an Investigator of the Howard Hughes Medical Institute.

Publisher Copyright:
© 2016 Elsevier Inc..


  • C. elegans
  • Excitation inhibition balance
  • Locomotion
  • Non-neuronal cells
  • Synapse maintenance

ASJC Scopus subject areas

  • Neuroscience (all)


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