美国布兰代斯大学Sengupta, Piali团队开发出肠神经元嗜离子受体调节盐胁迫抗性。2026年4月1日出版的《自然》杂志发表了这项成果。

在这里，该研究组发现I3咽肠神经元通过I3特异性的嗜离子受体对阳离子作出反应，以调节盐胁迫耐受性。GLR-9嗜离子受体和GLR-7 IR25a共受体同源物定位于肠腔暴露的I3感觉末端，是盐感觉的必要和充分条件。由于GLR-9突变体对高渗盐的耐受性降低，而对糖溶液的耐受性则降低，因此I3对盐的检测对高盐胁迫具有特异性保护作用。I3的胆碱能信号促进对急性高盐胁迫的耐受性，而I3在适应过程中的肽能信号对于抵抗随后的高盐挑战至关重要。转录组学和报告基因分析表明，I3部分通过调节远端组织中盐胁迫应答基因的表达来调节盐耐受性。相应的，盐和GLR-9调控基因子集的突变降低了盐胁迫抗性。他们的研究结果描述了由特定肠道神经元介导的化学感觉调节生理稳态以应对特定非生物应激的机制。

据介绍，通过内感受性化学感觉通路检测体内化学物质对调节代谢和生理至关重要。内感受器的分子特性，以及特定内感受器神经元的化学感觉的功能后果，仍有待充分描述。秀丽隐杆线虫的咽神经网络在解剖学和功能上类似于哺乳动物的肠神经系统。

附：英文原文

Title: An enteric neuron ionotropic receptor regulates salt stress resistance

Author: Yeon, Jihye, Kim, Jinmahn, Sato, Koji, Nurrish, Stephen, Chen, Laurie, Krishnan, Nikhila, Bates, Sam, Ihara, Sayoko, Rasouli, Sina, Porwal, Charmi, Venkatachalam, Vivek, Touhara, Kazushige, Sengupta, Piali

Issue&Volume: 2026-04-01

Abstract: The detection of internal chemicals by interoceptive chemosensory pathways is critical for regulating metabolism and physiology1. The molecular identities of interoceptors, and the functional consequences of chemosensation by specific interoceptive neurons, remain to be fully described. The pharyngeal neuronal network of Caenorhabditis elegans is anatomically and functionally analogous to the mammalian enteric nervous system2,3. Here we show that the I3 pharyngeal enteric neuron responds to cations via an I3-specific ionotropic receptor to regulate salt stress tolerance. The GLR-9 ionotropic receptor and the GLR-7 IR25a co-receptor orthologue localize to the gut lumen-exposed sensory ending of I3, and are necessary and sufficient for salt sensation. Salt detection by I3 protects specifically against high-salt stress, as glr-9 mutants show reduced tolerance of hypertonic salt but not of sugar solutions, with or without prior acclimatization. Whereas cholinergic signalling from I3 promotes tolerance of acute high-salt stress, peptidergic signalling from I3 during acclimatization is essential for resistance to a subsequent high-salt challenge. Transcriptomic and reporter gene analyses show that I3 modulates salt tolerance in part by regulating the expression of salt stress response genes in distal tissues. Correspondingly, mutations in a subset of salt- and GLR-9-regulated genes reduce salt stress resistance. Our results describe the mechanisms by which chemosensation mediated by a defined enteric neuron regulates physiological homeostasis in response to a specific abiotic stress.

DOI: 10.1038/s41586-026-10348-3

Source: https://www.nature.com/articles/s41586-026-10348-3