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辅助亚基调控发育中海马体NG2神经胶质细胞中AMPA受体复合物的功能及亚细胞分布。

Auxiliary Subunits Control Function and Subcellular Distribution of AMPA Receptor Complexes in NG2 Glia of the Developing Hippocampus.

作者信息

Hardt Stefan, Tascio Dario, Passlick Stefan, Timmermann Aline, Jabs Ronald, Steinhäuser Christian, Seifert Gerald

机构信息

Institute of Cellular Neurosciences, Medical Faculty, University of Bonn, Bonn, Germany.

出版信息

Front Cell Neurosci. 2021 Jun 10;15:669717. doi: 10.3389/fncel.2021.669717. eCollection 2021.

Abstract

Synaptic and axonal glutamatergic signaling to NG2 glia in white matter is critical for the cells' differentiation and activity dependent myelination. However, in gray matter the impact of neuron-to-NG2 glia signaling is still elusive, because most of these cells keep their non-myelinating phenotype throughout live. Early in postnatal development, hippocampal NG2 glia express AMPA receptors with a significant Ca permeability allowing for plasticity of the neuron-glia synapses, but whether this property changes by adulthood is not known. Moreover, it is unclear whether NG2 glia express auxiliary transmembrane AMPA receptor related proteins (TARPs), which modify AMPA receptor properties, including their Ca permeability. Through combined molecular and functional analyses, here we show that hippocampal NG2 glia abundantly express TARPs γ4, γ7, and γ8 as well as cornichon (CNIH)-2. TARP γ8 undergoes profound downregulation during development. Receptors of adult NG2 glia showed an increased sensitivity to blockers of Ca permeable AMPA receptors, but this increase mainly concerned receptors located close to the soma. Evoked synaptic currents of NG2 glia were also sensitive to blockers of Ca permeable AMPA receptors. The presence of AMPA receptors with varying Ca permeability during postnatal maturation may be important for the cells' ability to sense and respond to local glutamatergic activity and for regulating process motility, differentiation, and proliferation.

摘要

白质中向少突胶质前体细胞(NG2胶质细胞)的突触和轴突谷氨酸能信号传导对于细胞分化和活性依赖的髓鞘形成至关重要。然而,在灰质中,神经元与NG2胶质细胞信号传导的影响仍不清楚,因为这些细胞中的大多数在整个生命过程中都保持其非髓鞘形成表型。在出生后早期发育阶段,海马NG2胶质细胞表达具有显著钙通透性的AMPA受体,这使得神经元-胶质细胞突触具有可塑性,但这种特性在成年后是否会改变尚不清楚。此外,尚不清楚NG2胶质细胞是否表达辅助跨膜AMPA受体相关蛋白(TARPs),这些蛋白可改变AMPA受体特性,包括其钙通透性。通过结合分子和功能分析,我们在此表明海马NG2胶质细胞大量表达TARPsγ4、γ7和γ8以及卷曲螺旋蛋白(CNIH)-2。TARPγ8在发育过程中经历了显著下调。成年NG2胶质细胞的受体对钙通透性AMPA受体阻滞剂的敏感性增加,但这种增加主要涉及位于胞体附近的受体。NG2胶质细胞诱发的突触电流也对钙通透性AMPA受体阻滞剂敏感。出生后成熟过程中具有不同钙通透性的AMPA受体的存在可能对细胞感知和响应局部谷氨酸能活性的能力以及调节突起运动、分化和增殖很重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b671/8222826/cc394fbed494/fncel-15-669717-g001.jpg

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