MassIVEapplication/xmlftp://massive-ftp.ucsd.edu/v04/MSV000089032/primaryOK2000000ProteomicsAndrey CybulskyOrbitrap FusionMus Musculus (ncbitaxon:10090)https://massive.ucsd.edu/ProteoSAFe/dataset.jsp?task=cb39b8b589fe46deae24dac6b8f4252dandrey.cybulsky@mcgill.caDivision of Nephrology McGill University Health Centre Research InstituteMassIVE25MOD:01160 - "A protein modification that effectively results in the loss of an ammonia, usually by a process of vicinal dehydration, rearrangement, and rehydration with release of ammonia, resulting in a loss of nitrogen with no gain of oxygen."UNIMOD:35 - "Oxidation or Hydroxylation."Glomerular diseases involving podocyte/glomerular epithelial cell (GEC) injury feature protein misfolding and endoplasmic reticulum (ER) stress. Inositol-requiring enzyme 1α (IRE1α) mediates chaperone production and autophagy during ER stress. We examined the role of IRE1α in selective autophagy of the ER (reticulophagy). Control and IRE1α knockout (KO) GECs were incubated with tunicamycin to induce ER stress and subjected to proteomic analysis. This showed IRE1α-dependent upregulation of secretory pathway mediators, including the coat protein complex II component Sec23B. Tunicamycin enhanced expression of Sec23B and the reticulophagy adaptor reticulon-3-long (RTN3L) in control, but not IRE1α KO GECs. Knockdown of Sec23B reduced autophagosome formation in response to ER stress. Tunicamycin stimulated colocalization of autophagosomes with Sec23B and RTN3L in an IRE1α-dependent manner. Similarly, during ER stress, glomerular α5 collagen IV colocalized with RTN3L and autophagosomes. Degradation of RTN3L and collagen IV increased in response to tunicamycin, and the turnover was blocked by deletion of IRE1α; thus, the IRE1α pathway promotes RTN3L-mediated reticulophagy and collagen IV may be an IRE1α-dependent reticulophagy substrate. In experimental glomerulonephritis, expression of Sec23B, RTN3L, and LC3-II increased in glomeruli of control mice, but not in podocyte-specific IRE1α KO littermates. In conclusion, during ER stress, IRE1α redirects a subset of Sec23B-positive vesicles to deliver RTN3L-coated ER fragments to autophagosomes. Reticulophagy is a novel outcome of the IRE1α pathway in podocytes and may play a cytoprotective role in glomerular diseases.The unfolded protein response transducer IRE1α promotes reticulophagy in podocytes.Navarro-Betancourt José R JR, Papillon Joan J, Guillemette Julie J, Chung Chen-Fang CF, Iwawaki Takao T, Cybulsky Andrey V AVIre1p, Glomerular, Glomerular Visceral., ER-Phagy, Epithelial Cells, ER Phagy, Reticulophagy, Autophagy, Nucleophagy, Glomerular Visceral Epithelial Cells, 9030414B18Rik, Ire1alpha, Autophagocytosis, Podocyte, C85377, Cellular Autophagy, Cellular, Visceral Epithelial Cells, ER degradation, Lipophagy, Ire1a, AI225830, Ribophagy, endoplasmic reticulum degradationGlomerular Visceral., Unfolded Protein, ER-Phagy, Unfolded Protein Responses, Autophagy, Transducer, Visceral Epithelial Cells, ER degradation, Lipophagy, Unfolded, Ribophagy, endoplasmic reticulum degradation, Protein Response, Glomerular, Epithelial Cells, ER Phagy, Reticulophagy, Nucleophagy, Glomerular Visceral Epithelial Cells, Responses, Response, Autophagocytosis, Podocyte, Cellular Autophagy, Cellular, Protein Responsesbiochemical pathways, LC3/Atg8, single-organism catabolic process, multicellular organismal catabolic process, LC3A, Collagens, ER-Phagy, secretory pathway, atg8, Laboratory, Wound, Feature, Secretory Pathways, Secretion Pathway, Mus domesticus, Physical, Dambose, CASP-14, protein, injury, endoplasmic reticulum autophagy, House Mouse, prevention, trauma, Meat sugar, protein polypeptide chains, Glomerular, Secretory Processes, diseases, Mesoinositol, i-inositol, Roles, Endoplasmic Reticulum Stresses, 1, Concepts, 2, cellular degradation, diseases and disorders, 3, 4, 5, Zyderm, protein aggregate, prevention and control, Research-Related, CDA-II, Autophagosome, Atg8/LC3, increased, D-myo-Inositol, inosite, human disease, Tunicamycin, reference sample, catabolism, long, Microfibril Collagen Hemostat, L-myo-Inositol, hypoplasia, Swiss Mice, proteins, kidney glomerular epithelium, endoplasmic reticulum degradation, Atg8, 2R, preventive measures, LC3a, collagen, ER Phagy, Collagen Fleece, Nucleophagy, Role Concepts, ER-phagy, Podocyte, biotransformation, Homo sapiens disease, CDAN2, Collagen, podocyte, 3S, response to ER stress, preventive therapy, (1r, 6S)-cyclohexane-1, Glomerular nephritis, MAP1BLC3, Ergastoplasm, typical plasmatocyte, Injury and Wounds, mouse, Physical Traumas, macromolecule complex, cis-1, Glomerular Visceral, Ribophagy, Glomerulonephritides, CG32672, 6-hexol, Role Concept, ER stress, Playthings and Play, Reticulophagy, ER, Mini-ICE, Diseases, cellular response to endoplasmic reticulum stress, Autophagocytosis, Role, Plaything, Cellular, secretion, Physical Trauma, bright's disease, 5R, 4s, Mus musculus, 1L-myo-Inositol, breakdown, PAS formation, Caspase-14 subunit p10, 1D-myo-Inositol, Endoplasmic Reticulum, Autophagy, mice, Kidney, ER stress response, Swiss Mouse, Toys, Caspase-14 subunit p19, glomerular epithelial cell, Features, 5/4, MICE, experimental procedures, domesticus, disease, meso-Inositol, Glomerular Visceral Epithelial Cells, 6-HEXAHYDROXY-CYCLOHEXANE, Biocatalyst, CDAII, Research-Related Injuries, Reticulum Stresses, Collagen Felt, medical condition., Mouse, Research-Related Injury, accessory, Secretion Pathways, Secretion Process, epithelial cell of visceral layer of glomerular capsule, Research Related Injuries, 1010001H21Rik, 3.4.22.-, other disease, Plays, epithelium of glomerulus, 6-cyclohexanehexol, experimental, epithelium of kidney glomerulus, Biocatalysts, alpha-Collagen, Gene, Lipophagy, mini-ICE, protein-containing complex, Injuries and Wounds, supernumerary, cellular catabolism, LRRGT00047, Stresses, BcDNA:LD05816, ATG8a, autophagy of the ER, Microfibril, Wounds, polypeptide chain, reduced, House, Dermodress, Collastat, Gene Products, atg8a, disease or disorder, Cellular Autophagy, Mus musculus domesticus, ER Stress, MAP1ALC3, tiny, agranular plasmatocyte, ATG8E, Mice, Cyclohexitol, Toy, Chiro Inositol, Injury, methods, Playthings, breakdown of chemical, Swiss, experimental section, Phagophores, Avitene, blocked, ER autophagy, alpha Collagen, Scarring, HEMPAS, non-neoplastic, Enzyme, Puppets, Bright Disease, lamellocyte, Epithelial Cells, Traumas, Bios I, Play, disorder, Characteristics, Collagenfleece, Puppet, Controlled, small, cellular breakdown, Controlling, 4922501H04Rik, Reticulum Stress, degradation, protein complex, DmelCG32672, Proteins, disorders, 5-trans-4, ER degradation, medical condition, selective autophagy, LC3, Concept, Reticulum, Inositol, Characteristic, native protein, natural protein, traumatic injury, Wounds and Injury, Mus, renal glomerular podocyte, Trauma, Protein, proteomic analysis, Collagen Hemostat, condition, epithelium of renal glomerulus, Atg8A, Pangen, CG1534, breakdown of molecule, Secretion Processes, macromolecular complex, biodegradation, underdeveloped, prophylaxis, increased number, Ins, ER Stresses, other collagen, Chiro-Inositol, protein containing complex, Myoinositol, Visceral Epithelial Cells, wound, Avicon, DrAtg8a, House Mice, Anx3, Secretory Process, Injuries, Laboratory Mice, Protein Gene Products, Phagophore, Gene Proteins, present in greater numbers in organism, inositols, breakdown of substance, autophagy of the endoplasmic reticulum, autophagic vacuole formation, Endoplasmic, control, DEL, glomerular podocyte, Stress, granulocyte, Kidney Scarring, Laboratory Mouse, protein-protein complexIre1p, Glomerular, Glomerular Visceral., ER-Phagy, Epithelial Cells, ER Phagy, Reticulophagy, Autophagy, Nucleophagy, Glomerular Visceral Epithelial Cells, 9030414B18Rik, Ire1alpha, Autophagocytosis, Podocyte, C85377, Cellular Autophagy, Cellular, Visceral Epithelial Cells, ER degradation, Lipophagy, Ire1a, AI225830, Ribophagy, endoplasmic reticulum degradation0false IRE1alpha promotes reticulophagy in podocytes Protomics data for "IRE1alpha promotes reticulophagy in podocytes"Thu Mar 10 08:43:00 GMT 2022MSV00008903235304860