The Cell Adhesion Molecule Neurofascin Stabilizes Axo-axonic GABAergic Terminals at the Axon Initial Segment
The Cell Adhesion Molecule Neurofascin Stabilizes Axo-axonic GABAergic Terminals at the Axon Initial Segment
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DOI：
10.1074/jbc.m110.212191
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发表时间：
2011-07-08
影响因子：
4.8
通讯作者：
Volkmer, Hansjuergen
中科院分区：
文献类型：
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作者：
Kriebel, Martin;Metzger, Jennifer;Volkmer, Hansjuergen
细胞粘附分子通过细胞外相互作用和细胞内突触后支架组装的跨突触接触稳定化来调节突触的形成和维持。细胞粘附分子neurofascin定位于大鼠齿状回颗粒细胞的轴突起始段，主要被枝形细胞定位。慢病毒shRNA介导的成年大鼠脑中神经成束蛋白的敲低表明，神经成束蛋白调节突触后桥蛋白支架的数量和大小、GABA（A）受体簇的数量以及轴突起始段的突触前谷氨酸脱羧酶阳性终末。相比之下，海马神经元中神经成束蛋白的过表达可能通过刺激成纤维细胞生长因子受体1信号传导途径来增加桥蛋白簇的大小。
Cell adhesion molecules regulate synapse formation and maintenance via transsynaptic contact stabilization involving both extracellular interactions and intracellular postsynaptic scaffold assembly. The cell adhesion molecule neurofascin is localized at the axon initial segment of granular cells in rat dentate gyrus, which is mainly targeted by chandelier cells. Lentiviral shRNA-mediated knockdown of neurofascin in adult rat brain indicates that neurofascin regulates the number and size of postsynaptic gephyrin scaffolds, the number of GABA(A) receptor clusters as well as presynaptic glutamate decarboxylase-positive terminals at the axon initial segment. By contrast, overexpression of neurofascin in hippocampal neurons increases gephyrin cluster size presumably via stimulation of fibroblast growth factor receptor 1 signaling pathways.