Regulation of adult neural progenitor cell functions by purinergic signaling
Regulation of adult neural progenitor cell functions by purinergic signaling
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通过嘌呤能信号调节成体神经祖细胞功能
DOI：
10.1002/glia.23056
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发表时间：
2017-02
期刊：
影响因子：
--
通讯作者：
Peter Illes
中科院分区：
文献类型：
--
作者：
Yong Tang;Peter Illes
细胞外嘌呤是脑和脊髓的神经原性小生境中的信号分子，在那里它们激活胚胎神经干细胞（NSC）和成体神经祖细胞（NPC）的细胞表面嘌呤受体。尽管NSC/NPC中几乎所有的核苷酸敏感性P2 X/P2 Y和核苷敏感性腺苷受体亚型都表达mRNA和蛋白质，但只有少数具有功能意义。ATP被胞外核苷酸酶依次降解为ADP、AMP和腺苷，对不同的受体类别具有激动剂特性。核苷酸/核苷促进或抑制NSC/NPC增殖、迁移和分化。所有激动剂（尤其是ATP和ADP）最普遍的作用似乎是促进细胞增殖，通常通过P2 Y1 R，有时通过P2 X7 R。然而，通常P2 X7 R活化导致NPC的坏死/凋亡。分化可以通过P2 Y2 R激活或P2 X7 R阻断来启动。任一受体转导机制中的关键要素是细胞内游离Ca 2+浓度的增加，这可能是由于其从细胞内储存位点释放（G蛋白偶联; P2 Y）或由于其从细胞外空间通过受体通道本身（ATP门控离子通道; P2 X）而引起的。需要进一步的研究来阐明嘌呤能信号如何控制NSC/NPC的命运，以及如何通过精细和动态调节建立静态和激活状态之间的平衡。GLIA 2017;65：213-230
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. GLIA 2017;65:213–230
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