A Two-Immunoglobulin-Domain Transmembrane Protein Mediates an Epidermal-Neuronal Interaction to Maintain Synapse Density.
A Two-Immunoglobulin-Domain Transmembrane Protein Mediates an Epidermal-Neuronal Interaction to Maintain Synapse Density.
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DOI：
10.1016/j.neuron.2015.12.024
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发表时间：
2016-01-20
期刊：
影响因子：
16.2
通讯作者：
Jin Y
中科院分区：
文献类型：
--
作者：
Cherra SJ 3rd;Jin Y
突触的维持对神经回路的功能至关重要。在C.在elegans运动回路中，运动神经元与表皮直接接触。在这里，我们揭示了一种新的表皮神经元的相互作用介导的两个免疫球蛋白结构域的跨膜蛋白，ZIG-10，这是必要的维持胆碱能突触密度。ZIG-10定位于表皮和胆碱能运动神经元的细胞表面，在邻近突触的区域具有高水平。zig-10的缺失增加了胆碱能兴奋性突触的数量，并加剧了癫痫发作模型中的惊厥行为。GABA能抑制性神经元中zig-10的错误表达减少GABA能突触数量，这取决于表皮中ZIG-10的存在。此外，ZIG-10与酪氨酸激酶SRC-2相互作用以调节表皮的吞噬活性，从而限制胆碱能突触数量。我们的研究表明，非神经元细胞在调节神经回路功能中的高度特异性作用，通过神经元类型特异性维持突触密度。
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.