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

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27 Scopus citations

Abstract

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
JournalNeuron
Volume89
Issue number2
DOIs
StatePublished - 2016

Bibliographical note

Publisher Copyright:
© 2016 Elsevier Inc..

Keywords

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

ASJC Scopus subject areas

  • General Neuroscience

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