Activation of sodium-dependent glutamate transporters regulates the morphological aspects of oligodendrocyte maturation via signaling through calcium/calmodulin-dependent kinase IIβ's actin-binding/-stabilizing domain.
Activation of sodium-dependent glutamate transporters regulates the morphological aspects of oligodendrocyte maturation via signaling through calcium/calmodulin-dependent kinase IIβ's actin-binding/-stabilizing domain.
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DOI：
10.1002/glia.22699
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发表时间：
2014-09
期刊：
影响因子：
6.2
通讯作者：
Fuss, Babette
中科院分区：
文献类型：
--
作者：
Martinez-Lozada, Zila;Waggener, Christopher T.;Kim, Karam;Zou, Shiping;Knapp, Pamela E.;Hayashi, Yasunori;Ortega, Arturo;Fuss, Babette
经由主要兴奋性氨基酸谷氨酸的信号传导已经涉及少突胶质细胞（CNS的髓鞘形成细胞）生物学的各个方面的调节。在这方面，已描述少突胶质细胞谱系的细胞表达多种谷氨酸响应性跨膜蛋白，包括钠依赖性谷氨酸转运蛋白。后者已被充分表征为介导谷氨酸从细胞外空间的清除。然而，越来越多的证据表明，它们也介导谷氨酸诱导的细胞内信号传导事件。我们的数据显示，少突胶质细胞表达的钠依赖性谷氨酸转运蛋白，特别是GLT-1和GLAST的激活，促进少突胶质细胞成熟的形态学方面。发现这种效应与细胞内钙水平的瞬时增加和钙传感器钙/钙调蛋白依赖性激酶IIβ（CaMK II β）丝氨酸（S）371位点的瞬时磷酸化事件相关。潜在的调节S371位点位于CaMKIIβ先前定义的肌动蛋白结合/稳定结构域内，并且在我们的研究中，该结构域内的磷酸化事件被鉴定为钠依赖性谷氨酸转运蛋白介导的促进少突胶质细胞成熟的必要条件。此外，我们的数据为这些磷酸化事件在介导CaMKIIβ从丝状（F）-肌动蛋白脱离中的作用提供了很好的证据，从而允许少突胶质细胞的肌动蛋白细胞骨架的重塑。结合我们最近的研究结果，即CaMKIIβ在体内调节CNS髓鞘形成中的关键作用，我们的数据强烈表明钠依赖性谷氨酸转运蛋白-CaMKII β-肌动蛋白细胞骨架轴在少突胶质细胞成熟和CNS髓鞘形成的调节中起重要作用。
Signaling via the major excitatory amino acid glutamate has been implicated in the regulation of various aspects of the biology of oligodendrocytes, the myelinating cells of the CNS. In this respect, cells of the oligodendrocyte lineage have been described to express a variety of glutamate-responsive transmembrane proteins including sodium-dependent glutamate transporters. The latter have been well-characterized to mediate glutamate clearance from the extracellular space. However, there is increasing evidence that they also mediate glutamate-induced intracellular signaling events. Our data presented here show that activation of oligodendrocyte expressed sodium-dependent glutamate transporters, in particular GLT-1 and GLAST, promotes the morphological aspects of oligodendrocyte maturation. This effect was found to be associated with a transient increase in intracellular calcium levels and a transient phosphorylation event at the serine (S)371 site of the calcium sensor calcium/calmodulin-dependent kinase IIβ (CaMKIIβ). The potential regulatory S371 site is located within CaMKIIβ’s previously defined actin binding/stabilizing domain, and phosphorylation events within this domain were identified in our studies as a requirement for sodium-dependent glutamate transporter-mediated promotion of oligodendrocyte maturation. Furthermore, our data provide good evidence for a role of these phosphorylation events in mediating detachment of CaMKIIβ from filamentous (F)-actin, thereby allowing a remodeling of the oligodendrocyte’s actin cytoskeleton. Taken together with our recent findings, which demonstrated a crucial role of CaMKIIβ in regulating CNS myelination in vivo, our data strongly suggest that a sodium-dependent glutamate transporter-CaMKIIβ-actin cytoskeleton axis plays an important role in the regulation of oligodendrocyte maturation and CNS myelination.
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DOI：
10.1523/jneurosci.6129-08.2009
发表时间：
2009-06-17
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
DeSilva TM;Kabakov AY;Goldhoff PE;Volpe JJ;Rosenberg PA
通讯作者：
Rosenberg PA
DOI：
10.1523/jneurosci.2455-11.2011
发表时间：
2011-08-31
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
De Biase LM;Kang SH;Baxi EG;Fukaya M;Pucak ML;Mishina M;Calabresi PA;Bergles DE
通讯作者：
Bergles DE
影响因子：
158.5
作者：
Chang, A;Tourtellotte, WW;Trapp, BD
通讯作者：
Trapp, BD
影响因子：
3.4
作者：
Domercq, M;Sánchez-Gómez, MV;Matute, C
通讯作者：
Matute, C
影响因子：
6.2
作者：
DAMELIO, F;ENG, LF;GIBBS, MA
通讯作者：
GIBBS, MA