Clark H Smith Brain Tumour Centre, Arnie Charbonneau Cancer Institute, Alberta Children's Hospital Research Institute, and Department of Biochemistry and Molecular Biology Calgary, University of Calgary, Alberta, Canada.
PLoS Genet. 2022 Sep 1;18(9):e1010371. doi: 10.1371/journal.pgen.1010371. eCollection 2022 Sep.
The regulation of ribosome function is a conserved mechanism of growth control. While studies in single cell systems have defined how ribosomes contribute to cell growth, the mechanisms that link ribosome function to organismal growth are less clear. Here we explore this issue using Drosophila Minutes, a class of heterozygous mutants for ribosomal proteins. These animals exhibit a delay in larval development caused by decreased production of the steroid hormone ecdysone, the main regulator of larval maturation. We found that this developmental delay is not caused by decreases in either global ribosome numbers or translation rates. Instead, we show that they are due in part to loss of Rp function specifically in a subset of serotonin (5-HT) neurons that innervate the prothoracic gland to control ecdysone production. We find that these effects do not occur due to altered protein synthesis or proteostasis, but that Minute animals have reduced expression of synaptotagmin, a synaptic vesicle protein, and that the Minute developmental delay can be partially reversed by overexpression of synaptic vesicle proteins in 5-HTergic cells. These results identify a 5-HT cell-specific role for ribosomal function in the neuroendocrine control of animal growth and development.
核糖体功能的调节是一种保守的生长控制机制。虽然在单细胞系统中的研究已经定义了核糖体如何促进细胞生长，但将核糖体功能与生物体生长联系起来的机制还不太清楚。在这里，我们使用果蝇 Minutess（核糖体蛋白的杂合突变体）来探讨这个问题。这些动物表现出幼虫发育延迟，这是由于类固醇激素蜕皮激素（幼虫成熟的主要调节剂）产量减少引起的。我们发现，这种发育延迟不是由于核糖体数量或翻译率的普遍减少引起的。相反，我们表明，这部分是由于 Rp 功能的丧失，特别是在支配蜕皮激素产生的前胸腺神经纤维的 5-羟色胺（5-HT）神经元亚群中。我们发现这些影响不是由于蛋白质合成或蛋白质稳态的改变引起的，而是 Minute 动物中突触结合蛋白的表达减少，一种突触小泡蛋白，并且 5-HT 能细胞中突触小泡蛋白的过表达可以部分逆转 Minute 的发育延迟。这些结果确定了核糖体功能在神经内分泌控制动物生长和发育中的 5-HT 细胞特异性作用。
