C. elegans nucleostemin is required for larval growth and germline stem cell division.
C. elegans nucleostemin is required for larval growth and germline stem cell division.
复制标题
秀丽隐杆线虫核苷酸是幼虫生长和种系干细胞分裂所必需的。
DOI：
10.1371/journal.pgen.1000181
复制
发表时间：
2008-08-22
期刊：
影响因子：
4.5
通讯作者：
Reinke, Valerie
中科院分区：
文献类型：
--
作者：
Kudron, Michelle M.;Reinke, Valerie
核仁已被证明是与细胞生长和增殖相关的许多过程中不可或缺的。干细胞特别可能依赖于基于核仁的过程来保持增殖状态。一个高度保守的核仁因子nucleostemin被认为是核仁功能和干细胞特异性过程之间的关键环节。目前，还不清楚核干细胞蛋白是否通过影响核糖体生物合成或通过对干细胞和/或高度增殖细胞特异的另一种基于核仁的活性来调节增殖。本文研究了线虫C.这使我们能够在体内检测NST-1在增殖和分化过程中的功能。与哺乳动物核干细胞蛋白一样，NST-1蛋白定位于核仁和核质;然而，在分化和增殖细胞中均发现其表达。C.全球损失由于索马中的生长缺陷，秀丽线虫核干细胞蛋白（NST-1）导致幼虫停滞表型，而NST-1在生殖系中的特异性缺失导致生殖系干细胞经历细胞周期停滞。nst-1突变体显示rRNA水平降低，表明核糖体生物合成缺陷。然而，NST-1通常不存在于rRNA转录和加工发生的核仁区域，因此这种减少可能继发于核糖体生物合成中的不同缺陷。转基因研究表明，NST-1需要其N-末端结构域的稳定表达和G1 GT3和中间结构域的适当生殖系功能。我们的数据支持C的作用。nucleostemin通过促进核糖体的生物合成在细胞生长和增殖中起作用。干细胞在增殖和分化的交替命运之间小心地保持平衡。这种选择的调节是一个复杂的过程，发生在许多不同的层面上。控制这种选择的一个主要影响来自核仁发出的信号，核仁作为核糖体生物发生的位点和作为隔离的关键调节因子的储存库发挥双重作用。核仁中的GT3-nucleostemin最近已被确定为干细胞增殖和核仁功能之间的潜在联系，但其在核仁中的确切作用尚未在后生动物中直接解决。在这里，我们使用模式生物C。elegans研究nucleostemin在分化细胞和增殖干细胞中的功能。我们表明，核干细胞因子可能的行为，以调节核糖体的生物合成，并通过这一过程控制细胞增殖。我们还建议，至少在C。在线虫中，核干细胞蛋白的功能不限于增殖干细胞，而且它还在分化的细胞中起作用以控制细胞生长。我们的研究强调了核仁在调节细胞生长和分裂中的作用的复杂性。
The nucleolus has shown to be integral for many processes related to cell growth and proliferation. Stem cells in particular are likely to depend upon nucleolus-based processes to remain in a proliferative state. A highly conserved nucleolar factor named nucleostemin is proposed to be a critical link between nucleolar function and stem-cell–specific processes. Currently, it is unclear whether nucleostemin modulates proliferation by affecting ribosome biogenesis or by another nucleolus-based activity that is specific to stem cells and/or highly proliferating cells. Here, we investigate nucleostemin (nst-1) in the nematode C. elegans, which enables us to examine nst-1 function during both proliferation and differentiation in vivo. Like mammalian nucleostemin, the NST-1 protein is localized to the nucleolus and the nucleoplasm; however, its expression is found in both differentiated and proliferating cells. Global loss of C. elegans nucleostemin (nst-1) leads to a larval arrest phenotype due to a growth defect in the soma, while loss of nst-1 specifically in the germ line causes germline stem cells to undergo a cell cycle arrest. nst-1 mutants exhibit reduced levels of rRNAs, suggesting defects in ribosome biogenesis. However, NST-1 is generally not present in regions of the nucleolus where rRNA transcription and processing occurs, so this reduction is likely secondary to a different defect in ribosome biogenesis. Transgenic studies indicate that NST-1 requires its N-terminal domain for stable expression and both its G1 GTPase and intermediate domains for proper germ line function. Our data support a role for C. elegans nucleostemin in cell growth and proliferation by promoting ribosome biogenesis. Stem cells are carefully poised between the alternate fates of proliferation and differentiation. The regulation of this choice is a complex one that occurs on many different levels. One major influence controlling this choice derives signals emanating from the nucleolus, which serves dual roles as the site of ribosome biogenesis and as a repository for sequestered key regulatory factors. The nucleolar GTPase nucleostemin has recently been identified as a potential link between stem cell proliferation and nucleolar function, but its exact role in the nucleolus has not been directly addressed in a metazoan. Here, we use the model organism C. elegans to investigate the function of nucleostemin in both differentiated cells and proliferating stem cells. We show that nucleostemin probably acts to regulate ribosome biogenesis, and through this process controls cell proliferation. We also suggest that, at least in C. elegans, the function of nucleostemin is not restricted to proliferating stem cells, but that it also functions in differentiated cells to control cell growth. Our study highlights the complexity of the role of the nucleolus in regulation of cell growth and division.
登录
查看更多内容
影响因子：
12.3
作者：
通讯作者：
--
影响因子：
3.3
作者：
Ma, Hanhui;Pederson, Thoru
通讯作者：
Pederson, Thoru
影响因子：
64.5
作者：
AUSTIN, J;KIMBLE, J
通讯作者：
KIMBLE, J
影响因子：
56.9
作者：
Chen, X;Hiller, M;Fuller, MT
通讯作者：
Fuller, MT
影响因子：
64.8
作者：
Kruhlak, Michael;Crouch, Elizabeth E.;Casellas, Rafael
通讯作者：
Casellas, Rafael