title: A Two-Immunoglobulin-Domain Transmembrane Protein  Mediates an Epidermal-Neuronal Interaction to  Maintain Synapse Density.
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.
authors.affiliation: Section of Neurobiology, Division of Biological Sciences
authors.forename: Salvatore J
authors.initials: SJ
authors.lastname: Cherra
authors.forename: Yishi
authors.initials: Y
authors.lastname: Jin
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D004817:Epidermis / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism*
chemical_list: D029742:Caenorhabditis elegans Proteins; D007136:Immunoglobulins