The Sarcoglycan complex is expressed in the cerebrovascular system and is specifically regulated by astroglial Cx30 channels.

The Sarcoglycan complex is expressed in the cerebrovascular system and is specifically regulated by astroglial Cx30 channels.
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DOI:
10.3389/fncel.2015.00009
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发表时间:
2015
影响因子:
5.3
通讯作者:
Cohen-Salmon M
Cohen-Salmon M
中科院分区:
医学2区
文献类型:
--
作者:
Boulay AC;Saubaméa B;Cisternino S;Mignon V;Mazeraud A;Jourdren L;Blugeon C;Cohen-Salmon M

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星形胶质细胞是大脑中最突出的神经胶质细胞类型,在血管周围发送称为终足的专门过程,并表达调节脑血管系统生理学的大分子库。星形胶质细胞尾足最显著的特性之一是它们富含间隙连接蛋白43和30(Cx43和Cx 30),特别是允许离子和小信号分子通过血管周围星形胶质细胞网络的直接细胞间运输。在这项研究中,我们提出了具体的作用,Cx 30在胶质血管接口。使用Cx 30的失活小鼠模型(Cx 30 Δ/Δ; Δ表示缺失的等位基因),我们表明Cx 30的缺失不会影响血脑屏障(BBB)的组织和通透性。然而,它导致脑血管部分,编码γ-肌聚糖(γ-SG)的Sgcg强烈上调,γ-SG是连接细胞骨架和细胞外基质的肌营养不良蛋白相关蛋白复合物(DAPC)的成员。在Cx 30 T5 M/T5 M突变的小鼠中发生了相同的分子事件,其中Cx 30通道关闭,表明Sgcg调节依赖于Cx 30通道功能。我们进一步表征了脑血管系统中其他肌聚糖复合物(SGC)分子的表达,并显示存在α-、β-、δ-、γ-、ε-和β- SG以及Sarcospan。然而,它们的表达在Cx 30 Δ/Δ中没有改变。这些结果表明,在脑血管系统中可能存在完整的SGC,并且其成员之一γ-SG的表达依赖于Cx 30通道。如在骨骼肌中所述,SGC可能有助于脑血管系统中的膜稳定和信号转导,因此可能受Cx 30通道介导的功能调节。
Astrocytes, the most prominent glial cell type in the brain, send specialized processes called endfeet, around blood vessels and express a large molecular repertoire regulating the cerebrovascular system physiology. One of the most striking properties of astrocyte endfeet is their enrichment in gap junction proteins Connexin 43 and 30 (Cx43 and Cx30) allowing in particular for direct intercellular trafficking of ions and small signaling molecules through perivascular astroglial networks. In this study, we addressed the specific role of Cx30 at the gliovascular interface. Using an inactivation mouse model for Cx30 (Cx30Δ/Δ; Δ means deleted allele) we showed that absence of Cx30 does not affect blood-brain barrier (BBB) organization and permeability. However, it results in the cerebrovascular fraction, in a strong upregulation of Sgcg encoding γ-Sarcoglycan (γ-SG), a member of the Dystrophin-associated protein complex (DAPC) connecting cytoskeleton and the extracellular matrix. The same molecular event occurs in Cx30T5M/T5M mutated mice, where Cx30 channels are closed, demonstrating that Sgcg regulation relied on Cx30 channel functions. We further characterized the expression of other Sarcoglycan complex (SGC) molecules in the cerebrovascular system and showed the presence of α-, β-, δ-, γ-, ε- and ζ- SG, as well as Sarcospan. Their expression was however not modified in Cx30Δ/Δ. These results suggest that a full SGC might be present in the cerebrovascular system, and that expression of one of its member, γ-SG, depends on Cx30 channels. As described in skeletal muscles, the SGC may contribute to membrane stabilization and signal transduction in the cerebrovascular system, which may therefore be regulated by Cx30 channel-mediated functions.
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