Tamotsu Yoshimori

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..The role of autophagy in Staphylococcus aureus infection is also discussed...

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..The Atg14L-dependent appearance of PI3P in the ER makes this organelle the platform for autophagosome formation...

..These results demonstrate that dynamic membrane traffic mediates the sequential translocation and assembly of STING, both of which are essential processes required for maximal activation of the innate immune response triggered by dsDNA...

..These findings strongly suggest that the combinational SNARE proteins VAMP8 and Vti1b mediate the fusion of antimicrobial and canonical autophagosomes with lysosomes, an essential event for autophagic degradation...

..These findings reveal a unique survival strategy of HCV and provide new insights into the genotype-specific pathogenicity of HCV...

..These results show that the lipidation of LC3 paralogues is involved in the completion of autophagosome formation in mammalian cells. This study also provides a powerful tool for a wide variety of studies of autophagy in the future...

..These results provide new insight into organelle biogenesis by demonstrating that the ER-mitochondria contact site is important in autophagosome formation...

..We propose that the LC3 system is recruited through a mechanism that is independent of isolation membrane generation...

..These data suggest that the Beclin 1-hVps34 complex functions in two different steps of autophagy by altering the subunit composition...

..Furthermore, we show that Rubicon but not PLEKHM1 uniquely regulates membrane trafficking via simultaneously binding both Rab7 and PI3-kinase...

..Therefore, we propose that Atg16L1 T300A is differentially involved in Crohn disease and canonical autophagy...

..In other words, this situation provides the ER with the opportunity to recruit whatever proteins are in demand. Recently, we have uncovered how PtdIns(3)P is generated on the ER for the autophagic process...

..Electron tomography revealed that the ER-IM complex appears as a subdomain of the ER that formed a cradle encircling the IM, and showed that both ER and isolation membranes are interconnected...

..Electron tomography revealed the ER-IM complex as a subdomain of the ER forming a cradle encircling the IM, and showed that both ER and isolation membranes are interconnected...

..Local levels of PtdIns3P at the site of autophagosome formation determine autophagy initiation and the size of the autophagosome membrane structure...

..In addition, knockdown of these SNAREs inhibits the fusion of canonical autophagosomes with lysosomes. Together, these findings indicate that VAMP8 and Vti1b mediate fusion with lysosomes in both antimicrobial and canonical autophagy...

..PI3P is a key determinant of the autophagic membrane. Further, their relation to bactericidal autophagy (i.e. xenophagy) will be introduced...

..These methods will provide a relatively easy assessment of autophagy, and the details of the procedure will be described along with possible pitfalls...

..This finding will provide further important clues as to the origin of the autophagosome membrane, and how the process is regulated by starvation and PtdIns3P signals...

..Collectively, our data demonstrate the functional significance of autophagosome movement that enables effective delivery from the cytosol to lysosomes...

..Recent developments in this field suggest that the local PI3P concentration is dynamically regulated during autophagy, and that this molecule is critical to the proper control of autophagy...

..gingivalis MVs efficiently enter host cells via an endocytic pathway and survive within the endocyte organelles for an extended period, which provides better understanding of the role of MVs in the etiology of periodontitis...

..Concomitant inhibition of autophagy may be an attractive strategy for unlocking the antitumor potential of sorafenib in HCC...

..We propose that the Atg16L complex is a new type of E3-like enzyme that functions as a scaffold for LC3 lipidation by dynamically localizing to the putative source membranes for autophagosome formation...

..Here, we present a comprehensive overview of the putative membrane sources identified to date...

..Thus, ubiquitination seems to function as a general tag for selective autophagy in mammalian cells. This review discusses the present model of how autophagy sequesters invading bacteria through ubiquitination...

..We also showed that homotypic fusion of the initial GcAV leads to the formation of large GcAV, which is also unobserved in canonical autophagy...

..We propose that sustained tyrosine phosphorylation of EGFR facilitates its polyubiquitination in endosomes and counteracts rapid deubiquitination, thereby ensuring Hrs-dependent lysosomal sorting...

..These results demonstrate that Atg16L1 is an essential component of the autophagic machinery responsible for control of the endotoxin-induced inflammatory immune response...

..aureus were resistant to autophagic degradation. The present review focuses on the protective function of autophagy against bacterial invasion of cells...

..Enhancing autophagy may provide a novel therapeutic option to minimize AKI...

..We propose a novel model in which the mechanism of LC3 recruitment is separate from the generation of the isolation membrane. There exist at least three axes in Atg recruitment: ULK1 complex, Atg9L1, and Atg16L complex...

..Thus, the Beclin 1-Vps34-Vps15 complex functions in autophagy and the endocytic pathway, but its function in a given context depends on the identity of its interacting subunits...

..These results suggest that an Hsp90-dependent chaperone pathway incorporating hB-ind1 is involved in protein folding in the membranous web for the circumvention of the UPR and that it facilitates HCV replication...

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..This method will be of general utility for analysis of the autophagosome maturation process...

..These findings indicate that dynamic membrane trafficking is triggered by dsDNA stimulation and plays a pivotal role in the signal transduction required for optimal activation of the innate immune response...

..In autophagy-deficient Atg5-/- cells, GAS survived, multiplied, and were released from the cells. Thus, the autophagic machinery can act as an innate defense system against invading pathogens...

..These findings will now allow us to seek the possibility that the LM/LAM biosynthetic pathway is a chemotherapeutic target...

..In this review, we summarize the current understanding of how ATG proteins behave during autophagosome formation in both non-selective and selective autophagy...

..Therefore, autophagy is crucial for cellular defense against harmful materials inside cells...

..Taken together, these results indicate that hRME is primarily involved in membrane trafficking through early endosomes, but not through degradative organelles, such as multivesicular bodies and late endosomes...

..However, the autophagosomes induced by these bacteria have features distinct from those of the canonical pathway...

..All together, these data indicate that autophagy may be cytoprotective, at least under conditions of nutrient depletion, and point to an important cross talk between type 1 and type 2 cell death pathways...

..Generation of the form II correlates with autophagosome association of GABARAP and GATE16. These results suggest that all mammalian Atg8 homologues receive a common modification to associate with autophagosomal membrane as the form II...

..Recent studies have revealed insights into the molecular basis of membrane dynamics and the regulation of autophagy, which had remained cryptic for a long time...

..Based on these results, we propose a novel function of Hrs, as a crucial player in the maturation of autophagosomes...

..These results indicate that SKD1-dependent endosomal membrane trafficking is required for formation of autolysosomes...

..These results suggest that CHMP4b and Alix participate in formation of multivesicular bodies by cooperating with SKD1...

..To our knowledge, NDGA is the first case of a reagent that can modulate dynein-dynactin-related processes...

..By electron microscopy, similar structures can be found within autophagosomes. We propose that Alfy might target cytosolic protein aggregates for autophagic degradation...

..Intriguingly, the N-terminal coiled-coil region of mVps2 is required for the formation of the E235Q compartment but not for binding to SKD1. We propose that both SBP1 and mVps2 regulate SKD1 function in mammalian cells...

..Our results suggest that the regulation of autophagy is organ dependent and the role of autophagy is not restricted to the starvation response. This transgenic mouse model is a useful tool to study mammalian autophagy...

..These results add to the growing notion that the lipid droplet is an organelle endowed with more complex roles in various biological phenomena...

..Discovery of the Apg12 system has facilitated our understanding of the molecular mechanism of autophagosome formation...

..Because WD-repeat proteins provide a platform for protein-protein interactions, the approximately 800 kDa complex is expected to function in autophagosome formation, further interacting with other proteins in mammalian cells...

..These findings are now being applied to studies on the physiological roles of autophagy in mammals...

..We conclude that SKD1 regulates multiple steps of membrane transport out of early endosomes and the reformation of lysosomes from a hybrid organelle...

..This novel two-hybrid method, which we have named 'conjugation-mediated yeast two-hybrid', proves to be a simple and useful technique with which to analyze protein-protein conjugation...

..These results suggest that the production of amino acids by autophagic degradation of 'self' proteins, which allows for the maintenance of energy homeostasis, is important for survival during neonatal starvation...

..Rather, Shigella VirG, a protein required for intracellular actin-based motility, induced autophagy by binding to the autophagy protein, Atg5. In nonmutant Shigella, this binding is competitively inhibited by IcsB binding to VirG...

..Moreover, APG9L2 is a vertebrate-specific gene that may have gained critical roles in mammalian-specific developmental events, such as placentation, through rapid evolution...

..gingivalis adhesion to epithelial cells, while the subsequent uptake process requires lipid raft components for actin organization, with Rho GTPase Rac1...

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..In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to verify an autophagic response...

..Accordingly, simple comparison of LC3-I and LC3-II, or summation of LC3-I and LC3-II for ratio determinations, may not be appropriate, and rather, the amount of LC3-II can be compared between samples...

..In a mouse abscess model, the type II clones significantly induced serum IL-1beta and IL-6, as well as other infectious symptoms. These results suggest that type II fimbriae are a critical determinant of P. gingivalis virulence...

..Together, these findings demonstrate that ALIS act as generalized stress-induced protein storage compartments for substrates of the proteasome and autophagy...

..Moreover, inhibition of autophagy by 3-MA significantly facilitated B19-infection-mediated cell death. These results suggest a novel mechanism by which B19-infected cells survive by cellular autophagy...

..Therefore, CHMP5 regulates late endosome function downstream of MVB formation, and the loss of CHMP5 enhances signal transduction by inhibiting lysosomal degradation of activated receptors...

..Our findings support a role for autophagy in innate immunity and demonstrate that Salmonella infection is a powerful model to study the autophagy process...

..These results suggest that P. gingivalis accomplishes its internalization utilizing membrane lipid raft and cytoskeletal functions of the target cells...

..Therefore, we concluded that autophagy plays an important role in rimmed vacuole formation in certain muscular atrophies...