A5090861553- Autophagy in Disease and Therapy
- Cellular transport and secretion
- Mesenchymal stem cell research
- Endoplasmic Reticulum Stress and Disease
- Connexins and lens biology
- Calcium signaling and nucleotide metabolism
- Lysosomal Storage Disorders Research
- Periodontal Regeneration and Treatments
- Erythrocyte Function and Pathophysiology
- Osteoarthritis Treatment and Mechanisms
- Tendon Structure and Treatment
- Extracellular vesicles in disease
- RNA modifications and cancer
- Hepatitis C virus research
- Knee injuries and reconstruction techniques
- Neuroscience and Neuropharmacology Research
- Toxoplasma gondii Research Studies
- Muscle Physiology and Disorders
- Lipid Membrane Structure and Behavior
- Genetics and Neurodevelopmental Disorders
- Ion channel regulation and function
- Tissue Engineering and Regenerative Medicine
- Electrospun Nanofibers in Biomedical Applications
- Bone Tissue Engineering Materials
- NF-κB Signaling Pathways
Institute of Science Tokyo
2024-2025
Bioscience (China)
2025
Tokyo Medical and Dental University
2014-2024
Shanghai Institute for Science of Science
2024
The University of Tokyo
2020-2022
RIKEN Center for Brain Science
2009-2018
National Institute of Advanced Industrial Science and Technology
2006
Membrane fusion is generally controlled by Rabs, soluble N-ethylmaleimide–sensitive factor attachment protein receptors (SNAREs), and tethering complexes. Syntaxin 17 (STX17) was recently identified as the autophagosomal SNARE required for autophagosome–lysosome in mammals Drosophila. In this study, to better understand mechanism of fusion, we searched STX17-interacting proteins. Immunoprecipitation mass spectrometry analysis vacuolar sorting 33A (VPS33A) VPS16, which are components...
In macroautophagy, cytoplasmic contents are sequestered into the double-membrane autophagosome, which fuses with lysosome to become autolysosome. It has been thought that autophagy-related (ATG) conjugation systems required for autophagosome formation. Here, we found autophagosomal soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) syntaxin 17-positive autophagosome-like structures could be generated even in absence of ATG systems, although at a reduced rate. These...
Macroautophagy is an evolutionarily conserved catabolic mechanism that delivers intracellular constituents to lysosomes using autophagosomes. To achieve degradation, must fuse with closed We previously reported the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) syntaxin (STX) 17 translocates autophagosomes mediate fusion lysosomes. In this study, we report additional mechanism. found autophagosome-lysosome retained some extent even in STX17 knockout (KO) HeLa...
Macroautophagy is an intracellular degradation process that requires multiple autophagy-related (ATG) genes. In this study, we performed a genome-wide screen using the autophagic flux reporter GFP-LC3-RFP and identified TMEM41B as novel ATG gene. multispanning membrane protein localized in endoplasmic reticulum (ER). It has conserved domain also found vacuole 1 (VMP1), another ER essential for autophagy, yeast Tvp38, bacterial DedA family of putative half-transporters. Deletion blocked...
A ferritin particle consists of 24 proteins (FTH1 and FTL) stores iron ions within it. During deficiency, particles are transported to lysosomes release ions. Two transport pathways have been reported: macroautophagy ESCRT-dependent endosomal microautophagy. Although the membrane dynamics these differ, both require NCOA4, which is thought be an autophagy receptor for ferritin. However, it unclear whether NCOA4 only acts as in degradation. Here, we found that form liquid-like condensates a...
To develop stem cell therapy for small intestinal (SI) diseases, it is essential to determine whether SI cells in culture retain their tissue regeneration capabilities. By using a heterotopic transplantation approach, we show that cultured murine epithelial organoids are able reconstitute self-renewing epithelia the colon. When stably integrated, SI-derived grafts many features unique only but distinct from colonic epithelium. Our study provides evidence adult could be source of maintaining...
The lens of the eye is composed fiber cells, which differentiate from epithelial cells and undergo programmed organelle degradation during terminal differentiation. Although autophagy, a major intracellular system, constitutively active in these its physiological role has remained unclear. We have previously shown that Atg5-dependent macroautophagy not necessary for degradation, at least embryonic period. Here, we generated lens-specific Atg5 knock-out mice showed required any period life....
ATG2 is one of the autophagy‐related (ATG) proteins essential for autophagosome formation and localizes to isolation membranes lipid droplets in mammalian cells. Here, we investigated requirement regions ATG2A its organellar localization function. The N‐terminal amino acids 1–198 C‐terminal 1830–1938 are required droplets, respectively. region not autophagy. We also identified an amphipathic helix that both organelles formation. These data suggest dual regulated by different regions.
Aptamers are known for their higher discriminating ability between closely related molecules and requirement only a small region binding, as compared to an antibody. In the present studies, we have isolated specific RNA aptamer against influenza virus B/Johannesburg/05/1999 by in vitro selection procedure. The bound efficiently HA of B required 5 mM MgCl2 ion its recognition. not distinguished derived from A virus, but also inhibited HA-mediated membrane fusion.
Lipoproteins are lipid-protein complexes that primarily generated and secreted from the intestine, liver, visceral endoderm delivered to peripheral tissues. Lipoproteins, which assembled in endoplasmic reticulum (ER) membrane, released into ER lumen for secretion, but its mechanism remains largely unknown. Here, we show release of lipoproteins membrane requires VMP1, an transmembrane protein essential autophagy certain types secretion. Loss vmp1, not other autophagy-related genes, zebrafish...
Exosomes are small extracellular vesicles that originate from the intraluminal of multivesicular bodies (MVBs). We previously reported polarized Madin-Darby canine kidney (MDCK) epithelial cells secrete two types exosomes, apical and basolateral different MVBs. However, how these MVBs selectively targeted to or membrane remained unknown. Here, we analyze members Rab family GTPases show sets Rabs mediate asymmetrical exosome release. Rab27, best-known regulator MVB transport for release, is...
Abstract Hearing loss is the most frequent sensory disorder in humans. Auditory hair cells (HCs) are postmitotic at late-embryonic differentiation and postnatal stages, their damage major cause of hearing loss. There no measurable HC regeneration mammalian cochlea, maintenance cell function crucial for preservation hearing. Here we generated mice deficient autophagy-related 5 ( Atg5 ), a gene essential autophagy, HCs to investigate effect basal autophagy on acuity. Deletion resulted...
It has been suggested that prolonged inflammatory bowel diseases (IBD) may lead to colitis-associated carcinogenesis (CAC). We previously observed the NF-κB activation in colonic epithelial cells is associated with increased tumor necrosis factor receptor 2 (TNFR2) expression CAC development. However, mechanism by which leading still unclear. Myosin light chain kinase (MLCK) reported be responsible for permeability TNF signaling. Therefore we focused on role of MLCK via TNFR2 signaling...
Macroautophagy/autophagy, which is one of the main degradation systems in cell, mediated by a specialized organelle, autophagosome. Purification autophagosomes before fusion with lysosomes important for both mechanistic and physiological studies Here, we report simple method to accumulate undigested autophagosomes. Overexpression autophagosomal Qa-SNARE STX17 (syntaxin 17) lacking N-terminal domain (NTD) or N-terminally tagged GFP-STX17 causes accumulation A HeLa cell line, expresses...
Previous reports assumed that sphingomyelin (SM) is essential for HCV replication, but the mechanism was unclear. In this study, we showed first time SM and ceramide transfer protein (CERT), which in biosynthesis pathway, are of double-membrane vesicles (DMVs), sites viral replication. Low numbers DMVs were observed CERT-KO cells transfected with replicon RNA or constructs drive production a replication-independent system. replication rescued by ectopic expression CERT protein, not mutants,...
Rab5 and Rab7 are known to regulate endosome maturation, a Rab5-to-Rab7 conversion mediated by activator, Mon1-Ccz1, is essential for progression of the maturation process. However, importance mechanism inactivation during poorly understood. Here, we report novel Rab5-GAP, TBC1D18, which associated with Mon1 mediates maturation. We found that increased active (Rab5 hyperactivation) in addition reduced (Rab7 inactivation) occurs absence Mon1. present evidence showing severe defects Mon1-KO...
Differentiated muscle cells contain myofibrils and well-organized organelles, enabling powerful contractions. Muscle cell reorganization occurs in response to various physiological stimuli; however, the mechanisms behind this remodeling remain enigmatic due lack of a genetically trackable system. Previously, we reported that subset larval is remodeled into adult abdominal through an autophagy-dependent mechanism Drosophila . To unveil underlying remodeling, performed comparative time-course...
Differentiated muscle cells contain myofibrils and well-organized organelles, enabling powerful contractions. Muscle cell reorganization occurs in response to various physiological stimuli; however, the mechanisms behind this remodeling remain enigmatic due lack of a genetically trackable system. Previously, we reported that subset larval is remodeled into adult abdominal through an autophagy-dependent mechanism Drosophila . To unveil underlying remodeling, performed comparative time-course...
T-tubules are specialized invaginations of the plasma membrane essential for muscle contraction. While their physiological importance is well established, mechanisms underlying T-tubule formation remain elusive. Here, we identify LUBEL/RNF31, a ubiquitin E3 ligase responsible linear (M1-linked) ubiquitination, as key regulator biogenesis through proximity proteomics and RNAi screening in Drosophila. Loss LUBEL leads to Amphiphysin (Amph)-positive sheets instead tubular networks cells....
Tendons and ligaments are essential connective tissues that connect the muscle bone. Their recovery from injuries is known to be poor, highlighting crucial need for an effective therapy. A few reports have described development of artificial with sufficient strength human cells. In this study, we successfully generated a tendon-like tissue (bio-tendon) using induced pluripotent stem cells (iPSCs). We first differentiated iPSCs into mesenchymal (iPSC-MSCs) transfected them Mohawk (Mkx) obtain...
Background The M5 muscarinic acetylcholine receptor is known to play a crucial role in mediating dependent dilation of cerebral blood vessels. Previously, we reported that male knockout mice (M5R−/− mice) suffer from constitutive constriction arteries, reduced flow, dendritic atrophy, and short-term memory loss, without necrosis and/or inflammation the brain. Methodology/Principal Findings We employed Magnetic Resonance Angiography study area basilar artery female M5R−/− mice. Here show did...
It has been proposed that the hepatitis C virus (HCV) NS4B protein triggers membranous HCV replication compartment, but underlying molecular mechanism is not fully understood. Here, we screened for NS4B-associated membrane proteins by tandem affinity purification and proteome analysis identified 202 host proteins. Subsequent screening of replicon cells with small interfering RNA prolactin regulatory element binding (PREB) to be a novel cofactor. The interaction between PREB was confirmed...