Nitrate-responsive Sialin2 couples stress granule assembly and clearance to maintain neuronal homeostasis.

Authors

Xiaoyu Li, Zichen Cao, Ou Jiang, Songyue Wu, Bo Zhou, Yao Feng, Xinyue Chen, Jinsong Wang, Jian Zhou, Renhong Yan, Mo Chen, Songlin Wang

Published in

Developmental cell. Oct 02, 2026. Epub Oct 02, 2026.

Abstract

Stress granules (SGs) are phase-separated ribonucleoprotein condensates that support cellular adaptation to acute stress, but how extracellular signals coordinate their assembly and recovery-phase clearance remains unclear. Here, we show that nitrate-responsive Sialin2 coordinates SG homeostasis across the stress cycle. During acute stress, Sialin2 undergoes liquid-liquid phase separation and co-assembles with Ras GTPase-activating protein SH3-domain-binding protein (G3BP)-centered scaffolds to promote SG formation. During recovery, Sialin2 preserves liquid-like SG dynamics and promotes autophagy-linked clearance. Sialin2 loss delays SG resolution, promotes retention of amyotrophic lateral sclerosis (ALS)-linked fused in sarcoma (FUS) and TAR DNA-binding protein 43 (TDP-43) variants, and enhances amyloid precursor protein (APP)-related amyloidogenic output. In an ALS mouse model, nitrate treatment reduces SG-like pathology and neuroinflammation, preserves neuronal integrity, and delays functional decline. Together, these findings define a nitrate-Sialin2 signaling module that couples SG assembly to recovery-phase clearance and links inorganic anion sensing to protection against neurodegeneration.

PMID:
42826720
Bibliographic data and abstract were imported from PubMed on 03 Oct 2026.

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