Transcriptional Control of Synaptic Remodeling through Regulated Expression of an Immunoglobulin Superfamily Protein.
Transcriptional Control of Synaptic Remodeling through Regulated Expression of an Immunoglobulin Superfamily Protein.
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DOI：
10.1016/j.cub.2015.08.022
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发表时间：
2015-10-05
期刊：
影响因子：
--
通讯作者：
Miller DM 3rd
中科院分区：
文献类型：
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作者：
He S;Philbrook A;McWhirter R;Gabel CV;Taub DG;Carter MH;Hanna IM;Francis MM;Miller DM 3rd
神经回路在大脑发育过程中被积极重塑，但触发神经回路细化的分子机制却知之甚少。在这里，我们描述了秀丽隐杆线虫中的一个转录程序，该程序调节 Ig 结构域蛋白 OIG-1 的表达，以控制突触重塑的时间。 DD GABA 能神经元在幼虫发育过程中通过交换突触前和后成分的位置来反转极性。在新生幼虫中，DD 在背神经索中接收胆碱能输入。这些输入在第一个幼虫 (L1) 阶段结束时切换到腹侧。 VD 类 GABA 能神经元在 L1 晚期产生，位于背神经索中胆碱能神经元的突触后，但不重塑。我们利用乙酰胆碱受体 (AChR) 亚基 ACR-12::GFP 的靶向表达研究了 DD 和 VD 神经元中突触后装置的重塑。我们确定 OIG-1 拮抗 ACR-12 从 L1 DD 神经元背侧的重新定位。在 L1/L2 转换期间，DD 神经元中的 OIG-1 被转录因子 IRX-1/Iroquois 下调，从而使突触输入重新定位到腹侧。在通常不会重塑的 VD 类神经元中，转录因子 UNC-55/COUP-TF 会关闭 IRX-1，从而维持高水平的 OIG-1 以阻止背侧 ACR-12 受体的去除。 OIG-1 由 GABA 神经元分泌，但其抗可塑性功能是细胞自主的，但可能不需要分泌。我们的研究提供了一种新机制，通过 Ig 结构域蛋白的调节表达来启动突触重塑。
Neural circuits are actively remodeled during brain development but the molecular mechanisms that trigger circuit refinement are poorly understood. Here we describe a transcriptional program in C. elegans that regulates expression of an Ig domain protein, OIG-1, to control the timing of synaptic remodeling. DD GABAergic neurons reverse polarity during larval development by exchanging the locations of pre- and postsynaptic components. In newly born larvae, DDs receive cholinergic inputs in the dorsal nerve cord. These inputs are switched to the ventral side by the end of the first larval (L1) stage. VD class GABAergic neurons are generated in the late L1 and are postsynaptic to cholinergic neurons in the dorsal nerve cord but do not remodel. We investigated remodeling of the postsynaptic apparatus in DD and VD neurons using targeted expression of the acetylcholine receptor (AChR) subunit, ACR-12::GFP. We determined that OIG-1 antagonizes the relocation of ACR-12 from the dorsal side in L1 DD neurons. During the L1/L2 transition, OIG-1 is down-regulated in DD neurons by the transcription factor, IRX-1/Iroquois, allowing the repositioning of synaptic inputs to the ventral side. In VD class neurons, which normally do not remodel, the transcription factor UNC-55/COUP-TF turns off IRX-1, thus maintaining high levels of OIG-1 to block the removal of dorsally-located ACR-12 receptors. OIG-1 is secreted from GABA neurons but its anti-plasticity function is cell-autonomous but may not require secretion. Our study provides a novel mechanism by which synaptic remodeling is set in motion through regulated expression of an Ig domain protein.