Connexin-based channels contribute to metabolic pathways in the oligodendroglial lineage
Connexin-based channels contribute to metabolic pathways in the oligodendroglial lineage
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DOI：
10.1242/jcs.178731
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发表时间：
2016-05-01
影响因子：
4
通讯作者：
Xiao, Lan
中科院分区：
文献类型：
--
作者：
Niu, Jianqin;Li, Tao;Xiao, Lan
少突胶质前体细胞(OPC)经历了一系列耗能发育过程，但其能量代谢产物的摄取和转运途径尚不清楚。在本研究中，我们发现葡萄糖荧光类似物2-NBDG可以通过基于连接蛋白的缝隙连接通道在星形胶质细胞和少突胶质细胞之间传递，但不能在星形胶质细胞和OPC之间传递。相反，连接蛋白半通道介导的葡萄糖摄取支持OPC的增殖，而溴化乙锭摄取或2-NBDG摄取速率的增加与OPC细胞内钙的升高相关，表明连接蛋白半通道的钙依赖激活。有趣的是，星形胶质细胞中连接蛋白43(Cx43，也称为GJA1)的缺失通过降低基质葡萄糖水平而抑制OPC的增殖，而不影响OPC的半通道特性，这一过程也发生在急性脑片的胼胝体中。因此，连接蛋白通道的双重功能有助于少突胶质细胞的葡萄糖供应，这可能为能量代谢导向的少突胶质细胞靶向治疗铺平一条新的道路。
Oligodendrocyte precursor cells (OPCs) undergo a series of energy-consuming developmental events; however, the uptake and trafficking pathways for their energy metabolites remain unknown. In the present study, we found that 2-NBDG, a fluorescent glucose analog, can be delivered between astrocytes and oligodendrocytes through connexin-based gap junction channels but cannot be transferred between astrocytes and OPCs. Instead, connexin hemichannel-mediated glucose uptake supports OPC proliferation, and ethidium bromide uptake or increase of 2-NBDG uptake rate is correlated with intracellular Ca2+ elevation in OPCs, indicating a Ca2+-dependent activation of connexin hemichannels. Interestingly, deletion of connexin 43 (Cx43, also known as GJA1) in astrocytes inhibits OPC proliferation by decreasing matrix glucose levels without impacting on OPC hemichannel properties, a process that also occurs in corpus callosum from acute brain slices. Thus, dual functions of connexin-based channels contribute to glucose supply in oligodendroglial lineage, which might pave a new way for energy-metabolism-directed oligodendroglial-targeted therapies.