Nature：肠道中的膳食锌感受器，促进果蝇进食和生长
- ①在果蝇中鉴定出肠间质细胞表达的跨膜亲离子受体Hodor，在维持幼虫发育中有重要作用，特别是在营养缺乏的情况下；
- ②Hodor是可被锌离子激活的氯离子通道，介导了果蝇幼虫对于膳食锌的偏好；
- ③Hodor调节肠间质细胞的Tor信号和溶酶体功能，从而增加进食和激活脑中的胰岛素样信号，促进幼虫生长；
- ④Hodor参与维持肠腔的酸性环境、限制肠内微生物数量；
- ⑤Hodor样基因是昆虫特有的，或能作为蚊虫防控的药物靶点。
主编推荐语
锌是生物体所需的金属元素，Nature发表的一项最新研究，在果蝇中鉴定出一种表达在肠细胞中的锌感受器，通过调控进食和胰岛素样信号，来促进果蝇幼虫生长。这些发现为金属元素等微量营养元素调控宿主生长发育，提供了一种新机制。
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An intestinal zinc sensor regulates food intake and developmental growth
肠道的锌感受器调控进食和发育生长
10.1038/s41586-020-2111-5
2020-03-18, Article
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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.
First Authors:
Siamak Redhai,Clare Pilgrim
Correspondence Authors:
Irene Miguel-Aliaga
All Authors:
Siamak Redhai,Clare Pilgrim,Pedro Gaspar,Lena van Giesen,Tatiana Lopes,Olena Riabinina,Théodore 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
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