Control of hippocampal dendritic spine morphology through ephrin-A3/EphA4 signaling
Control of hippocampal dendritic spine morphology through ephrin-A3/EphA4 signaling
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DOI：
10.1038/nn994
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发表时间：
2003-02-01
影响因子：
25
通讯作者：
Pasquale, EB
中科院分区：
文献类型：
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作者：
Murai, KK;Nguyen, LN;Pasquale, EB
神经胶质细胞和神经元之间的通讯正在成为突触功能的关键参数。然而，人们对神经胶质细胞改变突触结构和生理学能力的分子机制知之甚少。在这里，我们描述了通过 EphA4 受体酪氨酸激酶及其配体肝配蛋白-A3 调节突触后形态的排斥相互作用。 EphA4 富集于成年小鼠海马锥体神经元的树突棘上，而肝配蛋白-A3 则定位于包围树突棘的星形胶质细胞突起上。研究发现，ephrin-A3 激活 EphA4 会诱导脊柱收缩，而抑制 ephrin/EphA4 相互作用会扭曲海马切片中的脊柱形状和组织。此外，EphA4 敲除小鼠的锥体神经元和用激酶失活的 EphA4 转染的切片中的脊柱不规则表明，肝配蛋白/EphA4 信号传导对于脊柱形态至关重要。因此，我们的数据支持一个模型，其中肝配蛋白-A3配体和EphA4受体之间的瞬时相互作用通过神经胶质细胞串扰调节兴奋性突触连接的结构。
Communication between glial cells and neurons is emerging as a critical parameter of synaptic function. However, the molecular mechanisms underlying the ability of glial cells to modify synaptic structure and physiology are poorly understood. Here we describe a repulsive interaction that regulates postsynaptic morphology through the EphA4 receptor tyrosine kinase and its ligand ephrin-A3. EphA4 is enriched on dendritic spines of pyramidal neurons in the adult mouse hippocampus, and ephrin-A3 is localized on astrocytic processes that envelop spines. Activation of EphA4 by ephrin-A3 was found to induce spine retraction, whereas inhibiting ephrin/EphA4 interactions distorted spine shape and organization in hippocampal slices. Furthermore, spine irregularities in pyramidal neurons from EphA4 knockout mice and in slices transfected with kinase-inactive EphA4 indicated that ephrin/EphA4 signaling is critical for spine morphology. Thus, our data support a model in which transient interactions between the ephrin-A3 ligand and the EphA4 receptor regulate the structure of excitatory synaptic connections through neuroglial cross-talk.