Targets of TGF-β signaling in Caenorhabditis elegans dauer formation

Targets of TGF-β signaling in Caenorhabditis elegans dauer formation
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DOI:
10.1006/dbio.1999.9545
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发表时间:
2000-01-01
影响因子:
2.7
通讯作者:
Thomas, JH
Thomas, JH
中科院分区:
生物学3区
文献类型:
--
作者:
Inoue, T;Thomas, JH

文献摘要

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秀丽隐杆线虫的形成受多种环境因素的控制。化学感觉神经元ASI通过分泌β 1 -7/TGF-β调节dauer形成,但β 1 -7配体的分子靶点不完全确定,细胞靶点未知。我们对一个被称为daf-14的假定的信号转导子进行了基因鉴定和克隆,发现它编码一个Smad蛋白。DAF-14 Smad具有非常不寻常的结构,完全缺乏迄今为止已知的所有其他Smad蛋白中发现的N-末端结构域,daf-14与daf-8遗传相互作用,后者编码另一种Smad,并且这种相互作用表明这两种Smad蛋白之间存在部分功能冗余。我们还通过研究daf-14和daf-4(假定的DAF-7受体)的作用位点,研究了daf-7信号传导的细胞靶点。DAF-14::GFP在Dauer形成期间重塑的多种组织中表达。然而,自由复制丢失和组织特异性表达构建体产生的镶嵌分析表明,daf-e的细胞非自主功能反对直接的DAF-7信号传导到整个动物的组织。相反,这些实验表明,神经系统是β-7信号传导的靶点,神经系统反过来又调节其他组织的dauer形成。(C)北京大学出版社.
Caenorhabditis elegans dauer formation is controlled by multiple environmental factors. The chemosensory neuron ASI regulates dauer formation by secretion of DAF-7/TGF-beta, but the molecular targets of the DAF-7 ligand are incompletely defined and the cellular targets are unknown. We genetically characterized and cloned a putative transducer of DAF-7 signaling called daf-14 and found that it encodes a Smad protein. DAF-14 Smad has a highly unusual structure completely lacking the N-terminal domain found in all other Smad proteins known to date, daf-14 genetically interacts with daf-8, which encodes another Smad, and the interaction suggests partial functional redundancy between these two Smad proteins. We also studied the cellular targets of DAF-7 signaling by studying the sites of action of daf-14 and daf-4, the putative receptor for DAF-7. daf-14::gfp is expressed in multiple tissues that are remodeled during dauer formation. However, analysis of mosaics generated by free duplication loss and tissue-specific expression constructs indicate cell-nonautonomous function of daf-e arguing against direct DAF-7 signaling to tissues throughout the animal. Instead, these experiments suggest the nervous system as a target of DAF-7 signaling and that the nervous system in turn regulates dauer formation by Other tissues. (C) 2000 Academic Press.