Regulation of endoplasmic reticulum turnover by selective autophagy
| Autor: | Paolo Grumati, Fulvio Reggiori, Muriel Mari, Aliaksandr Khaminets, Mario Mauthe, Antje K. Huebner, Britta Qualmann, Theresa Heinrich, Masato Akutsu, Nicole Koch, Sandor Nietzsche, Ingo Kurth, Ivan Dikic, Istvan Katona, Joachim Weis, Lutz Liebmann, Alexandra Stolz, Christian A. Hübner |
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| Přispěvatelé: | Microbes in Health and Disease (MHD), Center for Liver, Digestive and Metabolic Diseases (CLDM), Khaminets, Aliaksandr, Heinrich, Theresa, Mari, Muriel, Grumati, Paolo, Huebner, Antje K, Akutsu, Masato, Liebmann, Lutz, Stolz, Alexandra, Nietzsche, Sandor, Koch, Nicole, Mauthe, Mario, Katona, Istvan, Qualmann, Britta, Weis, Joachim, Reggiori, Fulvio, Kurth, Ingo, Hübner, Christian A, Dikic, Ivan |
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Nucleophagy
Male PROTEIN Apoptosis Biomarkers/metabolism Lysosomes/metabolism Endoplasmic Reticulum Mice Phagosomes Non-U.S. Gov't PHOSPHORYLATION Membrane Protein Phagosome Sensory Receptor Cells/metabolism Apoptosis Regulatory Protein Multidisciplinary Research Support Non-U.S. Gov't Intracellular Signaling Peptides and Proteins Adaptor Proteins LOCALIZATION Lysosome Endoplasmic Reticulum/chemistry Cell biology Neoplasm Proteins Biochemistry Microtubule-Associated Proteins/metabolism MACHINERY Female Autophagy/physiology Microtubule-Associated Proteins Human Protein Binding Phagosomes/metabolism Membrane Proteins/deficiency Sensory Receptor Cells GABARAP Reticulophagy Editorials: Cell Cycle Features Biology Research Support Cell Line Neoplasm Protein Neoplasm Proteins/deficiency Autophagy Journal Article Animals Humans Endomembrane system Adaptor Proteins Signal Transducing Animal Endoplasmic reticulum Microtubule-Associated Protein Signal Transducing Apoptosi Membrane Proteins Biomarker DEGRADATION SALMONELLA Adaptor Proteins Signal Transducing/metabolism Ion homeostasis ER Intracellular Signaling Peptides and Protein Reticulon CELLS Apoptosis Regulatory Proteins Lysosomes Biomarkers Gene Deletion |
| Zdroj: | Nature, 522(7556), 354-358. Nature Publishing Group Khaminets, A, Heinrich, T, Mari, M, Grumati, P, Huebner, A K, Akutsu, M, Liebmann, L, Stolz, A, Nietzsche, S, Koch, N, Mauthe, M, Katona, I, Qualmann, B, Weis, J, Reggiori, F, Kurth, I, Hübner, C A & Dikic, I 2015, ' Regulation of endoplasmic reticulum turnover by selective autophagy ', Nature, vol. 522, no. 7556, pp. 354-8 . https://doi.org/10.1038/nature14498 |
| ISSN: | 0028-0836 |
| DOI: | 10.1038/nature14498 |
| Popis: | The endoplasmic reticulum (ER) is the largest intracellular endomembrane system, enabling protein and lipid synthesis, ion homeostasis, quality control of newly synthesized proteins and organelle communication(1). Constant ER turnover and modulation is needed to meet different cellular requirements and autophagy has an important role in this process(2-8). However, its underlying regulatory mechanisms remain unexplained. Here we show that members of the FAM134 reticulon protein family are ER-resident receptors that bind to autophagy modifiers LC3 and GABARAP, and facilitate ER degradation by autophagy ('ER-phagy'). Downregulation of FAM134B protein in human cells causes an expansion of the ER, while FAM134B overexpression results in ER fragmentation and lysosomal degradation. Mutant FAM134B proteins that cause sensory neuropathy in humans(9) are unable to act as ER-phagy receptors. Consistently, disruption of Fam134b in mice causes expansion of the ER, inhibits ER turnover, sensitizes cells to stress-induced apoptotic cell death and leads to degeneration of sensory neurons. Therefore, selective ER-phagy via FAM134 proteins is indispensable for mammalian cell homeostasis and controls ER morphology and turnover in mice and humans. |
| Databáze: | OpenAIRE |
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