Ablation of Cx47 in transgenic mice leads to the loss of MUPP1, ZONAB and multiple connexins at oligodendrocyte-astrocyte gap junctions.
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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DOI：
10.1111/j.1460-9568.2008.06431.x
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发表时间：
2008-10
期刊：
影响因子：
--
通讯作者：
Nagy JI
中科院分区：
文献类型：
--
作者：
Li X;Penes M;Odermatt B;Willecke K;Nagy JI
中枢神经系统的少突胶质细胞通过异型间隙连接与星形胶质细胞连接，异型间隙连接由少突胶质细胞中的Cx32和Cx47以及星形胶质细胞中的Cx30和Cx43组成。这些间隙连接也含有调节蛋白，包括ZO-1和ZONAB。在这里，我们研究了多pdz结构域蛋白1 （MUPP1）在这些间隙连接中的定位，并检测了Cx47敲除小鼠中与少突胶质细胞相关的辅助蛋白和连接蛋白。在测试的每个中枢神经系统区域，在野生型小鼠的所有少突胶质细胞体细胞上都发现了点状免疫标记MUPP1。在少突胶质细胞-星形胶质细胞（O/A）间隙连接处，这些mupp1阳性点与少突胶质细胞Cx32或Cx47的点标记共定位，与星形胶质细胞-星形胶质细胞间隙连接处的星形胶质细胞Cx30或Cx43的点标记共定位，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，少突胶质细胞上没有MUPP1和ZONAB的免疫标记，而一些zo -1阳性点仍然存在。在Cx32基因敲除小鼠中，MUPP1和ZONAB在O/A间隙连接处持续存在。在Cx47敲除小鼠中，Cx47的缺失伴随着少突胶质细胞体细胞上Cx30、Cx32和Cx43的点状标记的完全丧失，以及Cx32沿髓鞘纤维的免疫标记的急剧增加。这些结果表明MUPP1在O/A间隙连接和cx47依赖的连接蛋白靶向少突胶质细胞体细胞的质膜上。此外，在Cx47基因敲除小鼠中报道的髓鞘形成缺陷似乎不仅源于Cx47的缺失，还源于少突胶质细胞体细胞间隙连接及其调节蛋白的缺失，并且Cx47的缺失可能部分通过沿髓鞘纤维的Cx32水平升高来补偿。
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 co-localized 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 of 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 by elevated levels of Cx32 along myelinated fibers.
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影响因子：
3.3
作者：
Li, X;Ionescu, AV;Nagy, JI
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