Tohoku University · Immunology and Microbiology
Professor Yoshihiko Kuchitsu's research lab focuses on the molecular mechanisms underlying intracellular membrane trafficking, particularly the regulation of autophagy and innate immune signaling. The lab investigates how key regulators such as Rab7 and STING control organelle dynamics, including autophagosome-lysosome fusion, lysosomal degradation, and the spatial organization of immune signaling complexes. Using advanced imaging techniques like Airyscan super-resolution microscopy and correlative light-electron microscopy, the lab uncovers the subcellular logistics of cellular quality control and immune activation pathways. Their work bridges cell biology, immunology, and intracellular trafficking to understand how cells maintain homeostasis and respond to stress or infection.
Figures are computed from collected data and may differ slightly.
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
Rab7 (or Ypt7 in yeast) is one of the well-characterized members of the Rab family small GTPases, which serve as master regulators of membrane trafficking in eukaryotes. It localizes to late endosomes and lysosomes and has multiple functions in the autophagic pathway as well as in the endocytic pathway. Because Rab7/Ypt7 has previously been shown to regulate the autophagosome-lysosome fusion step in yeast and fruit flies (i.e., autophagosome accumulation has been observed in both Ypt7-knockout [
Autophagy is a self-catabolic process through which cellular components are delivered to lysosomes for degradation. There are three types of autophagy, i.e., macroautophagy, chaperone-mediated autophagy (CMA), and microautophagy. In macroautophagy, a portion of the cytoplasm is wrapped by the autophagosome, which then fuses with lysosomes and delivers the engulfed cytoplasm for degradation. In CMA, the translocation of cytosolic substrates to the lysosomal lumen is directly across the limiting m
Macroautophagy (simply called autophagy hereafter) is an intracellular degradation mechanism that is activated by nutrient starvation. Although it is well known that starvation induces autophagosome formation in an mTORC1-dependent manner, whether starvation also regulates autophagosome or autolysosome maturation was unclear. In the present study, we succeeded in demonstrating that starvation activates autolysosome maturation in mammalian cells. We found that knockout (KO) of Rab7 (herein referr
The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) innate immune pathway has emerged as a critical driver of inflammation in a variety of settings, such as virus infection, cellular stress, tissue damage, and aging. The pathway detects microbial and host-derived double-stranded DNA (dsDNA) in the cytosol and triggers the production of type I interferons and proinflammatory cytokines that help eliminate the invading pathogens. STING is a mobile protein. After its binding to
Our body is constantly exposed to pathogens and equipped with a highly elaborate immune system to fight against invading pathogens. The first line of defence is the innate immune system. It has evolved to detect conserved microbial molecular patterns, dubbed pathogen-associated molecular patterns (PAMPs), through pattern recognition receptors (PRRs). The binding of PRRs to PAMPs activates intracellular signalling cascades that lead to the expression of proinflammatory cytokines, Type I interfero
Stimulator of interferon genes (STING) is essential for the type I interferon response against a variety of DNA pathogens 1,2 . Upon emergence of cytosolic DNA, STING translocates from the endoplasmic reticulum (ER) to the Golgi where STING activates the downstream kinase TBK1, then to lysosome through recycling endosomes (REs) for its degradation 3–6 . Although the molecular machinery of STING activation is extensively studied and defined 7 , the one underlying STING degradation has not yet bee
Abstract Stimulator of interferon genes (STING) is critical for the type I interferon response to pathogen- or self-derived cytosolic DNA. STING is degraded by the endosomal sorting complexes required for transport (ESCRT)-driven lysosomal microautophagy (LMA), the impairment of which leads to sustained inflammatory responses. It has been unknown how ESCRT targets STING directly to lysosomes. Here, through kinase inhibitor screening and knockdown experiments of all the individual components of E
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