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首页> 外文期刊>Glia >Regulation of Adult Neural Progenitor Cell Functions by Purinergic Signaling
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Regulation of Adult Neural Progenitor Cell Functions by Purinergic Signaling

机译:用嘌呤能信号调节成年神经祖细胞功能

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摘要

Extracellular purines are signaling molecules in the neurogenic niches of the brain and spinal cord, where they activate cell surface purinoceptors at embryonic neural stem cells (NSCs) and adult neural progenitor cells (NPCs). Although mRNA and protein are expressed at NSCs/NPCs for almost all subtypes of the nucleotide-sensitive P2X/P2Y, and the nucleoside-sensitive adenosine receptors, only a few of those have acquired functional significance. ATP is sequentially degraded by ecto-nucleotidases to ADP, AMP, and adenosine with agonistic properties for distinct receptor-classes. Nucleotides/nucleosides facilitate or inhibit NSC/NPC proliferation, migration and differentiation. The most ubiquitous effect of all agonists (especially of ATP and ADP) appears to be the facilitation of cell proliferation, usually through P2Y1Rs and sometimes through P2X7Rs. However, usually P2X7R activation causes necrosis/apoptosis of NPCs. Differentiation can be initiated by P2Y2R-activation or P2X7R-blockade. A key element in the transduction mechanism of either receptor is the increase of the intracellular free Ca2+ concentration, which may arise due to its release from intracellular storage sites (G protein-coupling; P2Y) or due to its passage through the receptor-channel itself from the extracellular space (ATP-gated ion channel; P2X). Further research is needed to clarify how purinergic signaling controls NSC/NPC fate and how the balance between the quiescent and activated states is established with fine and dynamic regulation.
机译:细胞外嘌呤是在脑和脊髓的神经源性核桃中的信号分子,在那里它们在胚胎神经干细胞(NSCs)和成人神经祖细胞(NPC)中激活细胞表面丙菌素。尽管MRNA和蛋白质在NSCs / NPC中表达几乎所有核苷酸敏感P2x / p2Y的亚型,以及核苷敏感的腺苷受体,只有少数人获得了功能性意义。 ATP被EECTO-核苷酸酶依次降解到ADP,AMP和腺苷,具有脱节的受体类的激动性质。核苷酸/核苷促进或抑制NSC / NPC增殖,迁移和分化。所有激动剂(特别是ATP和ADP)的最无处不在的效果似乎是细胞增殖的促进,通常通过P2Y1RS,有时通过P2X7RS。然而,通常p2x7r活化导致NPC的坏死/凋亡。分化可以通过P2Y2R激活或P2X7R阻滞来启动。任何受体的转导机制中的关键要素是细胞内游离Ca2 +浓度的增加,这可能由于其从细胞内储存位点(G蛋白偶联; P2Y)释放而产生或由于其通过受体沟道本身的通道而产生从细胞外空间(ATP门控离子通道; P2x)。需要进一步研究以阐明纯化的信号传导控制NSC / NPC命运以及如何使用细小和动态调节建立静态和激活状态之间的平衡。

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