Tohoku University · Immunology and Microbiology
Professor Kojiro Mukai's research lab focuses on the molecular mechanisms underlying innate immune signaling, particularly the regulation of the STING pathway in antiviral and anti-tumor immunity. The lab investigates how subcellular trafficking—especially retrograde transport via COP-I and post-translational modifications such as palmitoylation—control STING activation and its link to autoinflammatory diseases like COPA syndrome. Key research directions include the identification of STING as a cargo in intracellular transport, the role of organelle-specific modifications in immune activation, and the pathogenic consequences of disrupted protein trafficking in human disease. The lab integrates cell biology, immunology, and structural biology to uncover novel therapeutic targets for immune disorders and cancer.
Figures are computed from collected data and may differ slightly.
Stimulator of interferon genes (STING) is essential for the type I interferon response against DNA pathogens. In response to the presence of DNA and/or cyclic dinucleotides, STING translocates from the endoplasmic reticulum to perinuclear compartments. However, the role of this subcellular translocation remains poorly defined. Here we show that palmitoylation of STING at the Golgi is essential for activation of STING. Treatment with palmitoylation inhibitor 2-bromopalmitate (2-BP) suppresses pal
Coat protein complex I (COP-I) mediates the retrograde transport from the Golgi apparatus to the endoplasmic reticulum (ER). Mutation of the COPA gene, encoding one of the COP-I subunits (α-COP), causes an immune dysregulatory disease known as COPA syndrome. The molecular mechanism by which the impaired retrograde transport results in autoinflammation remains poorly understood. Here we report that STING, an innate immunity protein, is a cargo of the retrograde membrane transport. In the presence
DNA is present in the nucleus and mitochondria of eukaryotic cells. There are, however, certain instances in which DNA emerges in the cytosol. The two major sources of cytosolic DNA are self DNA that is leaked out from the nucleus or mitochondria, and non-self DNA from DNA viruses. The cytosolic DNA triggers the host immune response. Recent studies have identified two key molecules, cyclic GMP-AMP (cGAMP) synthase (cGAS) and stimulator of interferon genes (STING) in this immune response. STING i
Coat protein complex I (COP-I) mediates the retrograde transport from the Golgi to the ER 1,2 . Mutation of the COPA gene, encoding one of the COP-I subunits (α-COP), causes an immune dysregulatory disease (COPA syndrome) 3 . The molecular mechanism by which the impaired retrograde transport results in autoinflammation is not understood. Here we report that STING 4 , an innate immunity protein, is a cargo of the Golgi-to-ER membrane transport. In the presence of the disease-causative α-COP varia
Coat protein complex I (COP‐I) mediates the retrograde transport from the Golgi apparatus to the endoplasmic reticulum (ER). Mutation of the COPA gene, encoding one of the COP‐I subunits (α‐COP), causes an immune dysregulatory disease known as COPA syndrome. The molecular mechanism by which the impaired retrograde transport results in autoinflammation remains poorly understood. Here we report that STING, an innate immunity protein, is a cargo of the retrograde membrane transport. In the presence
Abstract Stimulator of interferon genes (STING) is essential for the type I interferon response against DNA pathogens. In response to the presence of DNA and/or cyclic dinucleotides, STING translocates from the endoplasmic reticulum to perinuclear compartments. However, the role of this subcellular translocation remains poorly defined. Here we show that palmitoylation of STING at the Golgi is essential for activation of STING. Treatment with palmitoylation inhibitor 2-bromopalmitate (2-BP) suppr
Abstract Stimulator of interferon genes (STING) is essential for the type I interferon response induced by microbial DNA from virus or self-DNA from mitochondria/nuclei. In response to emergence of such DNAs in the cytosol, STING translocates from the endoplasmic reticulum (ER) to the Golgi, and activates TANK-binding kinase 1 (TBK1) at the trans-Golgi network (TGN). Activated TBK1 then phosphorylates STING at Ser365, generating an interferon regulatory factor 3 (IRF3)-docking site on STING. How
Abstract Stimulator of interferon genes (STING) is an innate immune protein for DNA pathogens. In response to the emergence of DNA in the cytosol, STING relocates from the endoplasmic reticulum (ER) to the Golgi and induces the type I interferon response through cytosolic TANK-binding kinase 1 (TBK1). The molecular mechanism underlying TBK1 activation by STING remains poorly understood. Here we report a cell system by which STING and TBK1 are simultaneously monitored. The system utilizes STING/T
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