In Vivo Regulation of Oligodendrocyte Precursor Cell Proliferation and Differentiation by the AMPA-Receptor Subunit GIuA2
In Vivo Regulation of Oligodendrocyte Precursor Cell Proliferation and Differentiation by the AMPA-Receptor Subunit GIuA2
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DOI：
10.1016/j.celrep.2018.09.066
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发表时间：
2018-10-23
期刊：
影响因子：
8.8
通讯作者：
Kukley, Maria
中科院分区：
文献类型：
--
作者：
Chen, Ting-Jiun;Kula, Bartosz;Kukley, Maria
AMPA受体（AMPAR）介导的神经元和少突胶质前体细胞（OPCs）之间的突触信号传导的功能作用仍然是谜。我们通过靶向GIuA2亚基，在体内改变小鼠胼胝体轴突- opc突触ampar在髓鞘形成高峰期的特性。AMPARs中未编辑的（Ca2+可渗透的）或孔死亡的GIuA2亚基的表达可触发OPCs的增殖并减少其向少突胶质细胞的分化。GIuA2亚基（C-tail）的胞质c端（GIuA2(813862)）是一种旨在影响GIuA2与ampar结合蛋白之间相互作用并扰乱含有GIuA2的ampar运输的修饰，其表达降低了OPCs的分化而不影响其增殖。这些发现表明，OPCs中ampar的离子化和非离子化特性，以及小鼠胼胝体中ampar介导的轴突- opc突触信号传导的特定方面，对于平衡OPCs对增殖和分化信号的反应是重要的。
The functional role of AMPA receptor (AMPAR)mediated synaptic signaling between neurons and oligodendrocyte precursor cells (OPCs) remains enigmatic. We modified the properties of AMPARs at axon-OPC synapses in the mouse corpus callosum in vivo during the peak of myelination by targeting the GIuA2 subunit. Expression of the unedited (Ca2+ permeable) or the pore-dead GIuA2 subunit of AMPARs triggered proliferation of OPCs and reduced their differentiation into oligodendrocytes. Expression of the cytoplasmic C-terminal (GIuA2(813862)) of the GIuA2 subunit (C-tail), a modification designed to affect the interaction between GIuA2 and AMPAR-binding proteins and to perturb trafficking of GIuA2-containing AMPARs, decreased the differentiation of OPCs without affecting their proliferation. These findings suggest that ionotropic and non-ionotropic properties of AMPARs in OPCs, as well as specific aspects of AMPAR-mediated signaling at axon-OPC synapses in the mouse corpus callosum, are important for balancing the response of OPCs to proliferation and differentiation cues.