Regulation of store-operated and voltage-operated Ca2+ channels in the proliferation and death of oligodendrocyte precursor cells by golli proteins.
Regulation of store-operated and voltage-operated Ca2+ channels in the proliferation and death of oligodendrocyte precursor cells by golli proteins.
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DOI：
10.1042/an20090003
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发表时间：
2009-04-14
期刊：
影响因子：
4.7
通讯作者：
Campagnoni AT
中科院分区：
文献类型：
--
作者：
Paez PM;Fulton DJ;Spreuer V;Handley V;Campagnoni CW;Campagnoni AT
OPC（少突胶质细胞前体细胞）表达golli蛋白，通过调节Ca 2+内流，在OPC过程的延伸/收缩和迁移中起重要作用。本研究的目的是进一步研究golli在调节OPC发展中的作用。在从golli-KO（敲除）和JOE（golli J37过表达）小鼠制备的OPC的原代培养物中检查golli消融和过表达的影响。在缺乏golli或过度表达golli的OPCs中，生长因子撤回诱导的分化受损。在PDGF（血小板衍生生长因子）存在下的增殖分析显示，golli通过激活SOCC（钙池操纵的Ca 2+通道）增强有丝分裂原刺激的OPCs增殖。PDGF治疗诱导OPC细胞内Ca 2+的双相增加，并且golli在第二SOCC依赖性阶段期间特异性地增加Ca 2+内流，该阶段随后是Ca 2+从细胞内储存的初始释放。这种钙库操作的钙摄取似乎是细胞分裂所必需的，因为特定的SOCC拮抗剂完全阻断了PDGF和golli对OPC增殖的影响。此外，在过表达golli的OPCs中，在有丝分裂原撤除后观察到细胞死亡增加。这种现象可以通过暴露于VOCC（电压操纵的Ca 2+通道）阻断剂来防止，表明golli对细胞死亡的影响涉及通过VOCC增加Ca 2+内流。结果表明，golli对OPC的发展有明显的影响，并支持golli通过VOCCs和SOCCs调节多种Ca 2+调节事件的作用。我们的研究结果还表明，PDGF参与其受体导致OPC增殖通过激活SOCC进行。
OPCs (oligodendrocyte precursor cells) express golli proteins which, through regulation of Ca2+ influx, appear to be important in OPC process extension/retraction and migration. The aim of the present study was to examine further the role of golli in regulating OPC development. The effects of golli ablation and overexpression were examined in primary cultures of OPCs prepared from golli-KO (knockout) and JOE (golli J37-overexpressing) mice. In OPCs lacking golli, or overexpressing golli, differentiation induced by growth factor withdrawal was impaired. Proliferation analysis in the presence of PDGF (platelet-derived growth factor), revealed that golli enhanced the mitogen-stimulated proliferation of OPCs through activation of SOCCs (store-operated Ca2+ channels). PDGF treatment induced a biphasic increase in OPC intracellular Ca2+, and golli specifically increased Ca2+ influx during the second SOCC-dependent phase that followed the initial release of Ca2+ from intracellular stores. This store-operated Ca2+ uptake appeared to be essential for cell division, since specific SOCC antagonists completely blocked the effects of PDGF and golli on OPC proliferation. Additionally, in OPCs overexpressing golli, increased cell death was observed after mitogen withdrawal. This phenomenon could be prevented by exposure to VOCC (voltage-operated Ca2+ channel) blockers, indicating that the effect of golli on cell death involved increased Ca2+ influx through VOCCs. The results showed a clear effect of golli on OPC development and support a role for golli in modulating multiple Ca2+-regulatory events through VOCCs and SOCCs. Our results also suggest that PDGF engagement of its receptor resulting in OPC proliferation proceeds through activation of SOCCs.