STING signalling is terminated through ESCRT-dependent microautophagy of vesicles originating from recycling endosomes

STING炎症シグナルの終結分子機構 --新規細胞内分解システムの発見--. 京都大学プレスリリース. 2023-03-14.Stimulator of interferon genes (STING) is essential for the type I interferon response against a variety of DNA pathogens. Upon emergence of cytosolic DNA, STING translocates from the endoplasmic reticulum to the Golgi where STING activates the downstream kinase TBK1, then to lysosome through recycling endosomes (REs) for its degradation. Although the molecular machinery of STING activation is extensively studied and defined, the one underlying STING degradation and inactivation has not yet been fully elucidated. Here we show that STING is degraded by the endosomal sorting complexes required for transport (ESCRT)-driven microautophagy. Airyscan super-resolution microscopy and correlative light/electron microscopy suggest that STING-positive vesicles of an RE origin are directly encapsulated into Lamp1-positive compartments. Screening of mammalian Vps genes, the yeast homologues of which regulate Golgi-to-vacuole transport, shows that ESCRT proteins are essential for the STING encapsulation into Lamp1-positive compartments. Knockdown of Tsg101 and Vps4, components of ESCRT, results in the accumulation of STING vesicles in the cytosol, leading to the sustained type I interferon response. Knockdown of Tsg101 in human primary T cells leads to an increase the expression of interferon-stimulated genes. STING undergoes K63-linked ubiquitination at lysine 288 during its transit through the Golgi/REs, and this ubiquitination is required for STING degradation. Our results reveal a molecular mechanism that prevents hyperactivation of innate immune signalling, which operates at REs

Observation of gravitational waves from the coalescence of a 2.5–4.5 M ⊙ compact object and a neutron star

We report the observation of a coalescing compact binary with component masses 2.5–4.5 M ⊙ and 1.2–2.0 M ⊙ (all measurements quoted at the 90% credible level). The gravitational-wave signal GW230529_181500 was observed during the fourth observing run of the LIGO–Virgo–KAGRA detector network on 2023 May 29 by the LIGO Livingston observatory. The primary component of the source has a mass less than 5 M ⊙ at 99% credibility. We cannot definitively determine from gravitational-wave data alone whether either component of the source is a neutron star or a black hole. However, given existing estimates of the maximum neutron star mass, we find the most probable interpretation of the source to be the coalescence of a neutron star with a black hole that has a mass between the most massive neutron stars and the least massive black holes observed in the Galaxy. We provisionally estimate a merger rate density of 55−47+127Gpc−3yr−1 for compact binary coalescences with properties similar to the source of GW230529_181500; assuming that the source is a neutron star–black hole merger, GW230529_181500-like sources may make up the majority of neutron star–black hole coalescences. The discovery of this system implies an increase in the expected rate of neutron star–black hole mergers with electromagnetic counterparts and provides further evidence for compact objects existing within the purported lower mass gap

Observation of Gravitational Waves from the Coalescence of a 2.5−4.5 M⊙2.5-4.5~M_\odot Compact Object and a Neutron Star

International audienceWe report the observation of a coalescing compact binary with component masses $2.5-4.5~M_\odot$ and $1.2-2.0~M_\odot$ (all measurements quoted at the 90% credible level). The gravitational-wave signal GW230529_181500 was observed during the fourth observing run of the LIGO-Virgo-KAGRA detector network on 2023 May 29 by the LIGO Livingston Observatory. The primary component of the source has a mass less than $5~M_\odot$ at 99% credibility. We cannot definitively determine from gravitational-wave data alone whether either component of the source is a neutron star or a black hole. However, given existing estimates of the maximum neutron star mass, we find the most probable interpretation of the source to be the coalescence of a neutron star with a black hole that has a mass between the most massive neutron stars and the least massive black holes observed in the Galaxy. We estimate a merger rate density of $55^{+127}_{-47}~\text{Gpc}^{-3}\,\text{yr}^{-1}$ for compact binary coalescences with properties similar to the source of GW230529_181500; assuming that the source is a neutron star-black hole merger, GW230529_181500-like sources constitute about 60% of the total merger rate inferred for neutron star-black hole coalescences. The discovery of this system implies an increase in the expected rate of neutron star-black hole mergers with electromagnetic counterparts and provides further evidence for compact objects existing within the purported lower mass gap

Observation of Gravitational Waves from the Coalescence of a 2.5−4.5 M⊙2.5-4.5~M_\odot Compact Object and a Neutron Star

International audienceWe report the observation of a coalescing compact binary with component masses $2.5-4.5~M_\odot$ and $1.2-2.0~M_\odot$ (all measurements quoted at the 90% credible level). The gravitational-wave signal GW230529_181500 was observed during the fourth observing run of the LIGO-Virgo-KAGRA detector network on 2023 May 29 by the LIGO Livingston Observatory. The primary component of the source has a mass less than $5~M_\odot$ at 99% credibility. We cannot definitively determine from gravitational-wave data alone whether either component of the source is a neutron star or a black hole. However, given existing estimates of the maximum neutron star mass, we find the most probable interpretation of the source to be the coalescence of a neutron star with a black hole that has a mass between the most massive neutron stars and the least massive black holes observed in the Galaxy. We estimate a merger rate density of $55^{+127}_{-47}~\text{Gpc}^{-3}\,\text{yr}^{-1}$ for compact binary coalescences with properties similar to the source of GW230529_181500; assuming that the source is a neutron star-black hole merger, GW230529_181500-like sources constitute about 60% of the total merger rate inferred for neutron star-black hole coalescences. The discovery of this system implies an increase in the expected rate of neutron star-black hole mergers with electromagnetic counterparts and provides further evidence for compact objects existing within the purported lower mass gap

Observation of Gravitational Waves from the Coalescence of a 2.5–4.5 M _⊙ Compact Object and a Neutron Star

Abstract We report the observation of a coalescing compact binary with component masses 2.5–4.5 M ⊙ and 1.2–2.0 M ⊙ (all measurements quoted at the 90% credible level). The gravitational-wave signal GW230529_181500 was observed during the fourth observing run of the LIGO–Virgo–KAGRA detector network on 2023 May 29 by the LIGO Livingston observatory. The primary component of the source has a mass less than 5 M ⊙ at 99% credibility. We cannot definitively determine from gravitational-wave data alone whether either component of the source is a neutron star or a black hole. However, given existing estimates of the maximum neutron star mass, we find the most probable interpretation of the source to be the coalescence of a neutron star with a black hole that has a mass between the most massive neutron stars and the least massive black holes observed in the Galaxy. We provisionally estimate a merger rate density of 55 − 47 + 127 Gpc − 3 yr − 1 for compact binary coalescences with properties similar to the source of GW230529_181500; assuming that the source is a neutron star–black hole merger, GW230529_181500-like sources may make up the majority of neutron star–black hole coalescences. The discovery of this system implies an increase in the expected rate of neutron star–black hole mergers with electromagnetic counterparts and provides further evidence for compact objects existing within the purported lower mass gap.</jats:p