The cAMP response element binding protein (CREB) as an integrative HUB selector in metazoans: Clues from the hydra model system
The cAMP response element binding protein (CREB) as an integrative HUB selector in metazoans: Clues from the hydra model system
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DOI：
10.1016/j.biosystems.2006.09.014
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发表时间：
2007-02-01
期刊：
影响因子：
1.6
通讯作者：
Galliot, Brigitte
中科院分区：
文献类型：
--
作者：
Chera, Simona;Kaloulis, Kostas;Galliot, Brigitte
在真核细胞中，多种细胞外信号可以激活一个独特的信号转导系统，该系统在核水平上将打开各种靶基因，从而引发适应初始信号的不同反应。不同的信号如何能够汇聚在一个独特的信号通路上，而这个信号通路又会产生信号特异性的反应，这提供了一个可以追溯到进化早期的理论悖论。在双侧性哺乳动物中，CREB通路通过细胞质激酶将不同的细胞外信号连接到CREB转录因子和CBP共激活因子，根据上下文调节细胞存活、细胞增殖、细胞分化、促凋亡、长期记忆，从而实现细胞和发育过程的“枢纽”功能。在水螅中，CREB途径是高度保守的，并且在早期头部再生期间通过RSK依赖性CREB磷酸化而被激活。我们发现CREB转录因子和RSK激酶在所有三种水螅细胞谱系中共表达，包括分裂的间质干细胞、增殖的成精细胞、增殖的精原细胞和精母细胞、分化和成熟的神经元以及外胚层和内胚层肌上皮细胞。此外，CREB基因表达在早期再生和早期出芽期间特异性上调。当CREB功能被化学阻止时，不再观察到HyBraI基因的早期截肢后诱导，并且头部再生被堆积。因此，在水螅中，CREB途径似乎已经参与了多种任务，例如在成人背景下发育程序的重新激活，干细胞的自我更新，祖细胞的增殖和神经发生。因此，CREB通路发挥的中枢功能在动物进化的早期就已确立，并可能通过整合神经源性和模式化功能而有助于形成有效的口腔极。(c)2006爱思唯尔爱尔兰有限公司保留所有权利。
In eukaryotic cells, a multiplicity of extra-cellular signals can activate a unique signal transduction system that at the nuclear level will turn on a variety of target genes, eliciting thus diverse responses adapted to the initial signal. How distinct signals can converge on a unique signalling pathway that will nevertheless produce signal-specific responses provides a theoretical paradox that can be traced back early in evolution. In bilaterians, the CREB pathway connects diverse extra-cellular signals via cytoplasmic kinases to the CREB transcription factor and the CBP co-activator, regulating according to the context, cell survival, cell proliferation, cell differentiation, pro-apoptosis, long-term memory, hence achieving a "hub" function for cellular and developmental processes. In hydra, the CREB pathway is highly conserved and activated during early head regeneration through RSK-dependent CREB phosphorylation. We show here that the CREB transcription factor and the RSK kinase are co-expressed in all three hydra cell lineages including dividing interstitial stem cells, proliferating nematoblasts, proliferating spermatogonia and spermatocytes, differentiating and mature neurons as well as ectodermal and endodermal myoepithelial cells. In addition, CREB gene expression is specifically up-regulated during early regeneration and early budding. When the CREB function was chemically prevented, the early Post-amputation induction of the HyBraI gene was no longer observed and head regeneration was stacked. Thus, in hydra, the CREB pathway appears already involved in multiple tasks, such as reactivation of developmental programs in an adult context, self-renewal of stem cells, proliferation of progenitors and neurogenesis. Consequently, the hub function played by the CREB pathway was established early in animal evolution and might have contributed to the formation of an efficient oral pole through the integration of the neurogenic and patterning functions. (c) 2006 Elsevier Ireland Ltd. All rights reserved.