Potassium channel Kir4.1 regulates oligodendrocyte differentiation via intracellular pH regulation
Potassium channel Kir4.1 regulates oligodendrocyte differentiation via intracellular pH regulation
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DOI：
10.1002/glia.24240
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发表时间：
2022-07
期刊：
影响因子：
6.2
通讯作者：
Na Wang;Liang Zhou;Chong‐Yu Shao;Xin-Tai Wang;Nan Zhang;Jiao Ma;Hai-lan Hu;Yin Wang;M. Qiu;Ying Shen
中科院分区：
文献类型：
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作者：
Na Wang;Liang Zhou;Chong‐Yu Shao;Xin-Tai Wang;Nan Zhang;Jiao Ma;Hai-lan Hu;Yin Wang;M. Qiu;Ying Shen
在人类中，SeSAME/EAST综合征中Kcnj10的功能缺失突变导致进行性神经功能衰退，Kcnj10编码向内校正K+通道4.1 （Kir4.1）。尽管它在少突胶质细胞（OL）谱系细胞中丰富表达，并且与脱髓鞘疾病有新的联系，但Kir4.1在OL中的功能尚不清楚。在这里，我们展示了Kir4.1在OL发育中的新作用。Kir4.1在OL中的表达明显高于OL前体细胞（OPCs）， Kir4.1的下调通过影响OPC的分化来损害OL的成熟。有趣的是，Kir4.1通过Na+/H+交换器调节OPC和OLs的细胞内pH，这是Kir4.1抑制OPC分化的基础。此外，Kir4.1调控GSK3β和SOX10，这两个分子对OPC的发展至关重要。总的来说，我们的工作为理解Kir4.1和细胞内pH在OLs中的功能开辟了新的途径。
In humans, loss‐of‐function mutations of Kcnj10 in SeSAME/EAST syndrome, which encodes the inwardly rectifying K+ channel 4.1 (Kir4.1), causes progressive neurological decline. Despite its rich expression in oligodendrocyte (OL) lineage cells and an emerging link with demyelinating disease, the function of Kir4.1 in OLs is unclear. Here we show a novel role of Kir4.1 in OL development. Kir4.1 expression is markedly greater in OLs than in OL precursor cells (OPCs), and the down‐regulation of Kir4.1 impairs OL maturation by affecting OPC differentiation. Interestingly, Kir4.1 regulates the intracellular pH of OPCs and OLs via the Na+/H+ exchanger, which underlies impeded OPC differentiation by Kir4.1 inhibition. Furthermore, Kir4.1 regulates GSK3β and SOX10, two molecules critical to OPC development. Collectively, our work opens a new avenue to understanding the functions of Kir4.1 and intracellular pH in OLs.