Molecular machinery that terminates STING inflammation signaling

March 14, 2023

Novel mechanism for intracellular degradation discovered

Innate immunity is a natural mechanism to respond to foreign bodies. Stimulator of interferon genes (STING), localized in the endoplasmic reticulum, is an essential protein to prevent DNA virus infection. STING has been known to translocate to the Golgi apparatus upon DNA virus infection and activate an innate immune signaling. However, how the activated signaling is terminated has remained unknown. The collaborative research group, including Tohoku University, Fukushima Medical University, Kyoto University, and the RIKEN CSRS, demonstrated that the direct uptake and degradation of activated STING by lysosomes terminates the signaling.

This study result will lead to understanding the pathogenesis of inflammatory and neurodegenerative diseases and developing new treatments. Its application to the medical and pharmaceutical fields can be expected.

Original article
Nature Cell Biology doi:10.1038/s41556-023-01098-9
Y. Kuchitsu, K. Mukai, R. Uematsu, Y. Takaada, A. Shinojima, R. Shindo, T. Shoji, S. Hamano, E. Ogawa, R. Sato, K. Miyake, A. Kato, Y. Kawaguchi, M. Nishitani-Isa, K. Izawa, R. Nishikomori, T. Yasumi, T. Suzuki, N. Dohmae, T. Uemura, G. N. Barber, H. Arai, S. Waguri, T. Taguchi,
"STING signalling is terminated through ESCRT-dependent microautophagy of vesicles originating from recycling endosomes".
Naoshi Dohmae
Unit Leader
Biomolecular Characterization Unit