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首页> 外文期刊>The European Journal of Neuroscience >Ablation of Cx47 in transgenic mice leads to the loss of MUPP1, ZONAB and multiple connexins at oligodendrocyte-astrocyte gap junctions.
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Ablation of Cx47 in transgenic mice leads to the loss of MUPP1, ZONAB and multiple connexins at oligodendrocyte-astrocyte gap junctions.

机译:Cx47在转基因小鼠中的消融导致MUPP1,ZONAB和少突胶质细胞-星形胶质细胞间隙连接处的多种连接蛋白的损失。

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摘要

Oligodendrocytes in CNS are linked to astrocytes by heterotypic gap junctions composed of Cx32 and Cx47 in oligodendrocytes and Cx30 and Cx43 in astrocytes. These gap junctions also harbour regulatory proteins, including ZO-1 and ZONAB. Here, we investigated the localization of multi-PDZ domain protein 1 (MUPP1) at these gap junctions and examined accessory proteins and connexins associated with oligodendrocytes in Cx47-knockout mice. In every CNS region tested, punctate immunolabelling for MUPP1 was found on all oligodendrocyte somata in wild-type mice. These MUPP1-positive puncta were colocalized with punctate labelling for oligodendrocytic Cx32 or Cx47, and with astrocytic Cx30 or Cx43 at oligodendrocyte-astrocyte (O/A) gap junctions, but were not found at astrocyte-astrocyte gap junctions. In Cx47-knockout mice, immunolabelling of MUPP1 and ZONAB was absent on oligodendrocytes, whereas some ZO-1-positive puncta remained. In Cx32-knockout mice, MUPP1 and ZONAB persisted at O/A gap junctions. The absence of Cx47 in Cx47-knockout mice was accompanied by a total loss of punctate labelling for Cx30, Cx32 and Cx43 on oligodendrocyte somata, and by a dramatic increase in immunolabelling for Cx32 along myelinated fibers. These results demonstrate MUPP1 at O/A gap junctions and Cx47-dependent targeting of connexins to the plasma membranes of oligodendrocyte somata. Further, it appears that deficits in myelination reported in Cx47-knockout mice may arise not only from a loss of Cx47 but also from the accompanied loss of gap junctions and their regulatory proteins at oligodendrocyte somata, and that loss of Cx47 may be partly compensated for by elevated levels of Cx32 along myelinated fibers.
机译:CNS中的少突胶质细胞通过由少突胶质细胞中的Cx32和Cx47以及星形胶质细胞中Cx30和Cx43组成的异型间隙连接与星形胶质细胞连接。这些间隙连接也包含调节蛋白,包括ZO-1和ZONAB。在这里,我们研究了在这些间隙连接处的多PDZ域蛋白1(MUPP1)的定位,并检查了与Cx47敲除小鼠中少突胶质细胞相关的辅助蛋白和连接蛋白。在每个测试的中枢神经系统区域中,在野生型小鼠的所有少突胶质细胞体中都发现了MUPP1的点状免疫标记。这些MUPP1阳性小点与少突胶质Cx32或Cx47的点状标记共定位,并在少突胶质-星形胶质细胞(O / A)间隙连接处与星形胶质Cx30或Cx43共定位,但在星形胶质细胞-星形胶质细胞间隙连接处未发现。在Cx47基因敲除小鼠中,少突胶质细胞缺乏MUPP1和ZONAB的免疫标记,而一些ZO-1阳性点仍存在。在Cx32基因敲除小鼠中,MUPP1和ZONAB持续存在于O / A间隙连接处。在Cx47基因敲除小鼠中Cx47的缺失伴随着少突胶质细胞体上Cx30,Cx32和Cx43的点状标记的完全丧失,以及沿有髓纤维的Cx32免疫标记的显着增加。这些结果表明MUPP1在O / A间隙连接处和Cx47依赖的连接蛋白靶向少突胶质细胞体质膜。此外,似乎在Cx47基因敲除小鼠中报告的髓鞘缺乏症不仅可能是由于Cx47的缺失,而且还伴随着少突胶质细胞体的间隙连接及其调节蛋白的缺失,并且Cx47的缺失可能部分得到了补偿。沿有髓纤维的Cx32水平升高。

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