Multiple kinase pathways regulate voltage-dependent Ca2+ influx and migration in oligodendrocyte precursor cells.
Multiple kinase pathways regulate voltage-dependent Ca2+ influx and migration in oligodendrocyte precursor cells.
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DOI：
10.1523/jneurosci.5086-09.2010
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发表时间：
2010-05-05
期刊：
影响因子：
--
通讯作者：
Campagnoni AT
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文献类型：
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作者：
Paez PM;Fulton DJ;Spreur V;Handley V;Campagnoni AT
电压操纵性钙通道（voltage-operated Ca++ channels，VOCCs）在少突胶质细胞（oligodendrocyte progenitor cells，OPCs）的发育过程中起着重要作用。由于不同激酶的直接磷酸化是参与VOCC调节的最重要的机制之一，本研究的目的是评估丝氨酸/苏氨酸（Ser/Thr）激酶和酪氨酸激酶（TK）对VOCC介导的OPCs中Ca++内流的参与。钙成像显示OPCs通过L型VOCCs在质膜去极化后表现出Ca++内流。此外，VOCC介导的Ca++内流随着OPC分化而下降，表明VOCC在OPC中受到发育调控。PKC激活显著增加OPCs的VOCC活性，而PKA激活产生相反的效果。结果还表明，PKC激活引起的OPC形态学变化部分由VOCCs介导。我们的数据清楚地表明，TK对OPCs中的VOCC功能产生激活影响。此外，使用PDGF反应作为模型来探测TK受体（TKr）对OPCs Ca++摄取的作用，我们发现TKr激活增强了膜去极化后的Ca++内流。有趣的是，这种TKr对VOCC的调节似乎是PDGF增强OPC迁移率所必需的，因为在迁移测定中，细胞运动性被TKr拮抗剂以及VOCC抑制剂完全阻断。目前的研究有力地表明，PKC和TKrs增强OPCs的去极化诱导的Ca++内流，而PKA具有抑制作用。这些激酶调节OPCs中电压操作的Ca++摄取，并参与过程延伸和迁移的调节。
It is becoming increasingly clear that voltage-operated Ca++ channels (VOCCs) play a fundamental role in the development of oligodendrocyte progenitor cells (OPCs). Since direct phosphorylation by different kinases is one of the most important mechanisms involved in VOCC modulation, the aim of this study was to evaluate the participation of serine-threonine (Ser/Thr) kinases and tyrosine kinases (TK) on Ca++ influx mediated by VOCCs in OPCs. Calcium imaging revealed that OPCs exhibited Ca++ influx following plasma membrane depolarization via L-type VOCCs. Furthermore, VOCC-mediated Ca++ influx declined with OPC differentiation, indicating that VOCCs are developmentally regulated in OPCs. PKC activation significantly increased VOCC activity in OPCs, while PKA activation produced the opposite effect. The results also indicated that OPC morphological changes induced by PKC activation were partially mediated by VOCCs. Our data clearly suggest that TKs exert an activating influence on VOCC function in OPCs. Furthermore, using the PDGF response as a model to probe the role of TK receptors (TKr) on OPCs Ca++ uptake, we found that TKr activation potentiated Ca++ influx after membrane depolarization. Interestingly, this TKr modulation of VOCCs appeared to be essential for the PDGF enhancement of OPC migration rate, since cell motility was completely blocked by TKr antagonists, as well as VOCC inhibitors, in migration assays. The present study strongly demonstrates that PKC and TKrs enhance Ca++ influx induced by depolarization in OPCs, while PKA has an inhibitory effect. These kinases modulate voltage-operated Ca++ uptake in OPCs and participate in the modulation of process extension and migration.