小柯机器人

肠道锌离子感知蛋白可调节食物的摄入和发育生长
2020-03-19 15:27

英国MRC伦敦医学科学研究所Irene Miguel-Aliaga研究小组近日取得一项新成果。他们的研究发现一个肠道锌离子感知蛋白,其可调节食物的摄入和发育生长。2020年3月18日,《自然》杂志在线发表了这项成果。

研究人员使用果蝇遗传筛选鉴定到了Hodor蛋白,这是肠上皮细胞中的离子受体,可维持幼体发育,尤其是在缺乏营养的条件下。在非洲爪蟾卵母细胞和果蝇中进行的实验表明,Hodor是pH敏感的锌门控氯化物通道,可介导以前未知的锌饮食。Hodor通过促进食物摄入和胰岛素/IGF信号传导来控制部分肠上皮细胞(间质细胞)的系统生长。尽管Hodor维持肠腔内的酸度并抑制微生物负载,但其对系统生长的影响是由间质细胞内Tor信号传导和溶酶体稳态的调节产生的。
 
类似于Hodor的基因是昆虫特有的,可能是控制疾病媒介的靶标。此外,CRISPR–Cas9基因组编辑显示,冈比亚按蚊中唯一的Hodor直系同源物是必不可少的基因。这些发现表明,金属元素(更广泛地说是微量营养素)对能量稳态具有有益贡献。
 
据介绍,在细胞、器官和整个生物体中,营养感测是维持体内稳态和适应环境不断变化的关键。在许多动物中,科学家在消化系统的肠内分泌细胞中发现了营养传感器。然而,人们对吸收性肠上皮细胞中的营养感知仍知之甚少。
 
附:英文原文

Title: An intestinal zinc sensor regulates food intake and developmental growth

Author: Siamak Redhai, Clare Pilgrim, Pedro Gaspar, Lena van Giesen, Tatiana Lopes, Olena Riabinina, Thodore Grenier, Alexandra Milona, Bhavna Chanana, Jacob B. Swadling, Yi-Fang Wang, Farah Dahalan, Michaela Yuan, Michaela Wilsch-Brauninger, Wei-hsiang Lin, Nathan Dennison, Paolo Capriotti, Mara K. N. Lawniczak, Richard A. Baines, Tobias Warnecke, Nikolai Windbichler, Francois Leulier, Nicholas W. Bellono, Irene Miguel-Aliaga

Issue&Volume: 2020-03-18

Abstract: In cells, organs and whole organisms, nutrient sensing is key to maintaining homeostasis and adapting to a fluctuating environment1. In many animals, nutrient sensors are found within the enteroendocrine cells of the digestive system; however, less is known about nutrient sensing in their cellular siblings, the absorptive enterocytes1. Here we use a genetic screen in Drosophila melanogaster to identify Hodor, an ionotropic receptor in enterocytes that sustains larval development, particularly in nutrient-scarce conditions. Experiments in Xenopus oocytes and flies indicate that Hodor is a pH-sensitive, zinc-gated chloride channel that mediates a previously unrecognized dietary preference for zinc. Hodor controls systemic growth from a subset of enterocytes—interstitial cells—by promoting food intake and insulin/IGF signalling. Although Hodor sustains gut luminal acidity and restrains microbial loads, its effect on systemic growth results from the modulation of Tor signalling and lysosomal homeostasis within interstitial cells. Hodor-like genes are insect-specific, and may represent targets for the control of disease vectors. Indeed, CRISPR–Cas9 genome editing revealed that the single hodor orthologue in Anopheles gambiae is an essential gene. Our findings highlight the need to consider the instructive contributions of metals—and, more generally, micronutrients—to energy homeostasis.

DOI: 10.1038/s41586-020-2111-5

Source: https://www.nature.com/articles/s41586-020-2111-5

Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:43.07
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html


本期文章:《自然》:Online/在线发表

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