A novel nuclear signaling pathway for thromboxane A2 receptors in oligodendrocytes:: Evidence for signaling compartmentalization during differentiation
A novel nuclear signaling pathway for thromboxane A2 receptors in oligodendrocytes:: Evidence for signaling compartmentalization during differentiation
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DOI：
10.1128/mcb.00482-08
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发表时间：
2008-10-01
影响因子：
5.3
通讯作者：
Le Breton, Guy C.
中科院分区：
文献类型：
--
作者：
Mir, Fozia;Le Breton, Guy C.
本研究研究了少突胶质细胞（OLG）发育过程中G蛋白的表达、定位以及与血栓素A(2)受体（TPRs）的功能偶联。结果发现，随着OLGs的成熟，G(q)的表达量增加，而G（13）的表达量减少。相比之下，G(s)、G(o)和G(i)的表达水平没有明显变化。定位研究表明，G(q)、G（13）和G(i)只存在于核外室，而G(s)和G(o)在核外和核室中都存在。纯化的TPR-G蛋白复合物表明，tpr在核外室中与G(q)和G（13）偶联，但在核室中仅与G(s)偶联。此外，功能分析显示，刺激OLGs中的核TPR可刺激CREB磷酸化和髓鞘碱性蛋白转录，从而提高存活率。总的来说，这些结果表明：(i) OLGs在发育过程中选择性地调节某些G蛋白的表达，（ii） G蛋白在OLGs中存在差异定位，导致亚细胞区隔化，（iii） tpr在核外室中与G(q)和G（13）偶联，仅在细胞核中与G(s)偶联，（iv）成熟的OLGs具有功能性的核TPR-G(s)信号通路。核TPR信号可以刺激CREB磷酸化和髓磷脂基因转录，提高细胞存活率。这些发现代表了细胞发育过程中G蛋白偶联受体-G蛋白信号传导选择性调节的新范式。
The present study investigated G protein expression, localization, and functional coupling to thromboxane A(2) receptors (TPRs) during oligodendrocyte (OLG) development. It was found that as OLGs mature, the expression levels of G(q) increase while those of G(13) decrease. In contrast, the expression levels of G(s), G(o), and G(i) do not change significantly. Localization studies revealed that G(q), G(13), and G(i) are present only in the extranuclear compartment, whereas G(s) and G(o) are found in both the extranuclear and the nuclear compartments. Purification of TPR-G protein complexes demonstrated that TPRs couple to both G(q) and G(13) in the extranuclear compartment but only to G(s) in the nuclear compartment. Furthermore, functional analysis revealed that stimulation of nuclear TPR in OLGs stimulates CREB phosphorylation and myelin basic protein transcription and increases survival. Collectively, these results demonstrate that (i) OLGs selectively modulate the expression of certain G proteins during development, (ii) G proteins are differentially localized in OLGs leading to subcellular compartmentalization, (iii) TPRs couple to G(q) and G(13) in the extranuclear compartment and to G(s) only in the nucleus, (iv) mature OLGs have a functional nuclear TPR-G(s) signaling pathway, and ( v) nuclear TPR signaling can stimulate CREB phosphorylation and myelin gene transcription and increase cell survival. These findings represent a novel paradigm for selective modulation of G protein-coupled receptor-G protein signaling during cell development.