Glutamate stimulates oligodendrocyte progenitor migration mediated via an αv integrin/myelin proteolipid protein complex
Glutamate stimulates oligodendrocyte progenitor migration mediated via an αv integrin/myelin proteolipid protein complex
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DOI：
10.1523/jneurosci.4054-05.2006
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发表时间：
2006-03-01
影响因子：
5.3
通讯作者：
Macklin, WB
中科院分区：
文献类型：
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作者：
Gudz, TI;Komuro, H;Macklin, WB
在哺乳动物中枢神经系统中，少突胶质前体细胞(OPC)表达大多数神经递质受体，但其功能尚不清楚。目前的研究表明，谷氨酸(AMPA和/或海人藻酸)受体在OPC迁移中起着生理作用。AMPA通过增加细胞运动速度和钙瞬变频率来刺激α(V)整合素介导的OPC迁移。含有髓鞘蛋白脂蛋白(PLP)和α(V)整合素的蛋白质复合体调节AMPA刺激的迁移，刺激OPCAMPA受体导致AMPA受体亚基本身与α(V)整合素/PLP复合体的结合增加。因此，AMPA受体刺激后，形成α(V)整合素/PLP/神经递质受体蛋白复合体，减少与细胞外基质的结合，促进OPC迁移。为了评估PLP参与AMPA刺激的迁移的程度，分析了具有PLP基因突变的髓鞘缺陷(MD)大鼠的OPC。MD大鼠的OPC具有正常的基础迁移速率，但AMPA不能刺激这些细胞的迁移，提示PLP/α(V)整合素复合体在AMPA介导的诱导中起重要作用。尽管基线迁移是正常的，但AMPA对OPC迁移的调节可被百日咳毒素取消。因此，G蛋白依赖的信号转导对AMPA刺激的OPC迁移至关重要，但对OPC的基础迁移不起作用。参与AMPA刺激的OPC迁移的其他信号通路也被确定。这些研究强调了OPC迁移的新的信号决定因素，并提示谷氨酸可能在调节整合素介导的OPC迁移中发挥关键作用。
In the mammalian CNS, oligodendrocyte precursor cells (OPCs) express most neurotransmitter receptors, but their function remains unclear. The current studies suggest a physiological role for glutamate ( AMPA and/or kainate) receptors in OPC migration. AMPA stimulated alpha(v) integrin-mediated OPC migration by increasing both the rate of cell movement and the frequency of Ca2+ transients. A protein complex containing the myelin proteolipid protein (PLP) and alpha(v) integrin modulated the AMPA-stimulated migration, and stimulation of OPCAMPA receptors resulted in increased association of the AMPA receptor subunits themselves with the alpha(v) integrin/PLP complex. Thus, after AMPA receptor stimulation, an alpha(v) integrin/PLP/neurotransmitter receptor protein complex forms that reduces binding to the extracellular matrix and enhances OPC migration. To assess the extent to which PLP was involved in the AMPA-stimulated migration, OPCs from the myelin-deficient ( MD) rat, which has a PLP gene mutation, were analyzed. OPCs from the MD rat had a normal basal migration rate, but AMPA did not stimulate the migration of these cells, suggesting that the PLP/alpha(v) integrin complex was important for the AMPA-mediated induction. AMPA-induced modulation of OPC migration was abolished by pertussis toxin, although baseline migration was normal. Thus, G-protein-dependent signaling is crucial for AMPA-stimulated migration of OPCs but not for basal OPC migration. Other signaling pathways involved in this AMPA-stimulated OPC migration were also determined. These studies highlight novel signaling determinants of OPC migration and suggest that glutamate could play a pivotal role in regulating integrin-mediated OPC migration.