抑制核糖体在表皮中的生物发生足以引发秀丽隐杆线虫的全生物体生长停滞,而与营养状况无关。

IF 7.8 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY PLoS Biology Pub Date : 2023-08-31 eCollection Date: 2023-08-01 DOI:10.1371/journal.pbio.3002276
Qiuxia Zhao, Rekha Rangan, Shinuo Weng, Cem Özdemir, Elif Sarinay Cenik
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引用次数: 0

摘要

器官间的交流对多细胞生物的生长、发育和稳态至关重要。由于细胞消融方法的局限性,限制组织特异性生长改变的细胞非自主抑制性线索没有得到很好的表征。在这项研究中,我们利用秀丽隐杆线虫中生长素诱导的降解系统,通过消耗必需因子(RPOA-2、GRWD-1或TSR-2),在时间和空间上调节核糖体的生物发生。我们的研究结果表明,胚胎范围内对核糖体生物发生的抑制诱导了可逆的早期幼虫生长停滞,其特点是独特的基因表达特征不同于饥饿或衰老阶段。当核糖体的生物发生在体积相似的组织中受到抑制时,包括体壁肌肉、表皮、咽部、肠道或生殖系,会导致整个生物体不同程度的生长发育迟缓。我们表明,特异性抑制表皮中核糖体的生物发生足以引发整个生物体的生长停滞。表皮特异性核糖体缺失导致幼虫在L3阶段生长停滞,减少整个生物体的蛋白质合成,并诱导细胞非自主基因表达改变。进一步的分子分析揭示了分泌蛋白的过度表达,提示了整个生物体的调节机制。我们发现UNC-31是一种致密核心囊泡(DCV)通路成分,在表皮核糖体生物发生介导的生长停滞中发挥着重要作用。我们的组织特异性敲除实验表明,表皮特异性核糖体生物发生抑制诱导的全生物体生长停滞通过减少表皮中unc-31的表达而受到抑制,但在神经元或体壁肌肉中没有。类似地,IDA-1,DCV的膜相关蛋白,过表达,并且其在表皮中的敲低抑制了整个生物体的生长停滞,以响应表皮核糖体生物发生抑制。最后,我们观察到,当表皮核糖体生物发生受到抑制时,IDA-1标记的DCV点状点总体增加,并且这些点状点存在于表皮细胞中或附近。总之,这些发现表明了一种新的营养非依赖性多细胞生长协调机制,该机制始于核糖体生物发生抑制后的表皮组织。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Inhibition of ribosome biogenesis in the epidermis is sufficient to trigger organism-wide growth quiescence independently of nutritional status in C. elegans.

Interorgan communication is crucial for multicellular organismal growth, development, and homeostasis. Cell nonautonomous inhibitory cues, which limit tissue-specific growth alterations, are not well characterized due to cell ablation approach limitations. In this study, we employed the auxin-inducible degradation system in C. elegans to temporally and spatially modulate ribosome biogenesis, through depletion of essential factors (RPOA-2, GRWD-1, or TSR-2). Our findings reveal that embryo-wide inhibition of ribosome biogenesis induces a reversible early larval growth quiescence, distinguished by a unique gene expression signature that is different from starvation or dauer stages. When ribosome biogenesis is inhibited in volumetrically similar tissues, including body wall muscle, epidermis, pharynx, intestine, or germ line, it results in proportionally stunted growth across the organism to different degrees. We show that specifically inhibiting ribosome biogenesis in the epidermis is sufficient to trigger an organism-wide growth quiescence. Epidermis-specific ribosome depletion leads to larval growth quiescence at the L3 stage, reduces organism-wide protein synthesis, and induced cell nonautonomous gene expression alterations. Further molecular analysis reveals overexpression of secreted proteins, suggesting an organism-wide regulatory mechanism. We find that UNC-31, a dense-core vesicle (DCV) pathway component, plays a significant role in epidermal ribosome biogenesis-mediated growth quiescence. Our tissue-specific knockdown experiments reveal that the organism-wide growth quiescence induced by epidermal-specific ribosome biogenesis inhibition is suppressed by reducing unc-31 expression in the epidermis, but not in neurons or body wall muscles. Similarly, IDA-1, a membrane-associated protein of the DCV, is overexpressed, and its knockdown in epidermis suppresses the organism-wide growth quiescence in response to epidermal ribosome biogenesis inhibition. Finally, we observe an overall increase in DCV puncta labeled by IDA-1 when epidermal ribosome biogenesis is inhibited, and these puncta are present in or near epidermal cells. In conclusion, these findings suggest a novel mechanism of nutrition-independent multicellular growth coordination initiated from the epidermis tissue upon ribosome biogenesis inhibition.

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来源期刊
PLoS Biology
PLoS Biology 生物-生化与分子生物学
CiteScore
14.40
自引率
2.00%
发文量
359
审稿时长
3 months
期刊介绍: PLOS Biology is an open-access, peer-reviewed general biology journal published by PLOS, a nonprofit organization of scientists and physicians dedicated to making the world's scientific and medical literature freely accessible. The journal publishes new articles online weekly, with issues compiled and published monthly. ISSN Numbers: eISSN: 1545-7885 ISSN: 1544-9173
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