Coordinate pathways for nucleotide and EGF signaling in cultured adult neural progenitor cells
Coordinate pathways for nucleotide and EGF signaling in cultured adult neural progenitor cells
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DOI：
10.1242/jcs.044891
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发表时间：
2009-07-15
影响因子：
4
通讯作者：
Zimmermann, Herbert
中科院分区：
文献类型：
--
作者：
Grimm, Ivette;Messemer, Nanette;Zimmermann, Herbert
成年脑室下区（SVZ）含有星形胶质细胞样干细胞，能够为嗅球产生新的神经元。成体神经发生是由多种信号系统驱动的，这些信号系统可以诱导协同或相反的细胞反应。因此，重要的是要深入了解潜在的下游信号通路。我们以前已经表明，核苷酸ADP β S和UTP诱导培养的SVZ衍生的成人神经祖细胞的快速Ca 2+瞬变和增加生长因子介导的祖细胞增殖。在这里，我们研究了ADP β S，UTP和表皮生长因子（EGF）引起的信号通路。所有三种激动剂引起ERK 1/2和CREB磷酸化，但核苷酸和EGF之间的时间特性不同。祖细胞的分化改变了受体分布。少突胶质细胞和年轻的神经元，但不是星形胶质细胞，失去对激动剂的反应。抑制实验表明ADP β S诱导的EGF受体反式激活。UTP通过P2 Y（2）受体发挥作用，而ADP β S通过P2 Y（1）受体和P2 Y（13）受体发挥作用。我们的数据表明，核苷酸和EGF诱导收敛，但也有差异，细胞内信号通路，并建议他们携带的潜力，协同作用，在成人神经发生的细胞增殖和细胞存活的控制。
The adult subventricular zone (SVZ) contains astrocyte-like stem cells capable of generating new neurons for the olfactory bulb. Adult neurogenesis is driven by a variety of signal systems that can induce synergistic or opposing cellular responses. It is therefore important to gain insight into the underlying downstream signaling pathways. We have previously shown that the nucleotides ADP beta S and UTP induce rapid Ca2+ transients in cultured SVZ-derived adult neural progenitors and augment growth-factor-mediated progenitor cell proliferation. Here, we investigated signaling pathways elicited by ADP beta S, UTP and epidermal growth factor (EGF). All three agonists elicit ERK1/2 and CREB phosphorylation but the temporal characteristics differ between the nucleotides and EGF. Differentiation of the progenitors alters the receptor profile. Oligodendrocytes and young neurons, but not astrocytes, lose responsiveness to the agonists. Inhibition experiments are indicative of an ADP beta S-elicited EGF receptor transactivation. Whereas UTP acts via the P2Y(2) receptor, ADP beta S exerts its function via the P2Y(1) receptor and the P2Y(13) receptor. Our data demonstrate that nucleotides and EGF induce converging, but also differential, intracellular signaling pathways and suggest that they carry the potential to act synergistically in the control of cell proliferation and cell survival in adult neurogenesis.