致死量の塩を感知し防御反応を誘導する、新規な分子神経機構を発見――線虫は、腸で塩分を検知し、耐性遺伝子を発現制御することで、塩分環境に適応する――

2026-04-02 東京大学

研究成果の概要

＜関連情報＞

• https://www.a.u-tokyo.ac.jp/topics/topics_20260402-1.html
• https://www.nature.com/articles/s41586-026-10348-3

腸管神経のイオンチャネル型受容体は塩ストレス耐性を調節する An enteric neuron ionotropic receptor regulates salt stress resistance

Jihye Yeon,Jinmahn Kim,Koji Sato,Stephen Nurrish,Laurie Chen,Nikhila Krishnan,Sam Bates,Sayoko Ihara,Sina Rasouli,Charmi Porwal,Vivek Venkatachalam,Kazushige Touhara & Piali Sengupta}
Nature  Published:01 April 2026
DOI:https://doi.org/10.1038/s41586-026-10348-3

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 system^2,3. 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.