Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C1175175 (SARS)
19,188 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Autophagy is a cellular response to starvation that generates autophagosomes to carry long-lived proteins and cellular organelles to lysosomes for degradation. Activation of autophagy by viruses can provide an innate defense against infection, and for (+) strand RNA viruses autophagosomes can facilitate assembly of replicase proteins. We demonstrated that nonstructural protein (NSP) 6 of the avian coronavirus, infectious bronchitis virus (IBV), generates autophagosomes from the ER. A statistical analysis of MAP1LC3B puncta showed that NSP6 induced greater numbers of autophagosomes per cell compared with starvation, but the autophagosomes induced by NSP6 had smaller diameters compared with starvation controls. Small diameter autophagosomes were also induced by infection of cells with IBV, and by NSP6 proteins of MHV and SARS and NSP5, NSP6, and NSP7 of arterivirus PRRSV. Analysis of WIPI2 puncta induced by NSP6 suggests that NSP6 limits autophagosome diameter at the point of omegasome formation. IBV NSP6 also limited autophagosome and omegasome expansion in response to starvation and Torin1 and could therefore limit the size of autophagosomes induced following inhibition of MTOR signaling, as well as those induced independently by the NSP6 protein itself. MAP1LC3B-puncta induced by NSP6 contained SQSTM1, which suggests they can incorporate autophagy cargos. However, NSP6 inhibited the autophagosome/lysosome expansion normally seen following starvation. Taken together the results show that coronavirus NSP6 proteins limit autophagosome expansion, whether they are induced directly by the NSP6 protein, or indirectly by starvation or chemical inhibition of MTOR signaling. This may favor coronavirus infection by compromising the ability of autophagosomes to deliver viral components to lysosomes for degradation.
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PMID:Coronavirus NSP6 restricts autophagosome expansion. 2499 33

The endoplasmic reticulum (ER) is the main site of cellular protein and calcium homeostasis, as well as lipid synthesis in eukaryotic cells. Reticulophagy is the selective clearance and degradation of ER components and membranes by the cellular autophagy machinery. Recently, 2 groups (the laboratories of Noboru Mizushima and Wade Harper) independently identified the previously uncharacterized protein TEX264 (testis expressed gene 264) as a major receptor for selective reticulophagy in mammalian cells. Here we highlight and integrate the major findings of their recent work. Abbreviations: AIM: Atg8-interacting motif; AP-MS: affinity purification-mass spectrometry; ATL3: atlastin GTPase 3; Baf A1: bafilomycin A1; CCPG1: cell cycle progression 1; CRISPR: clustered regularly interspaced short palindromic repeats; GABARAP: gamma-aminobutyric acid receptor associated protein; GFP: green fluorescent protein; GyrI: gyrase inhibitor; IDR: intrinsically disordered region; IP: immunoprecipitation; KO: knockout; LIR: LC3-interacting region; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; MEF: mouse embryonic fibroblast; MS: mass spectrometry; MTOR: mechanistic target of rapamycin kinase; RB1CC1/FIP200: RB1-inducible coiled-coil 1; RFP: red fluorescent protein; RNAi: RNA interference; RTN3: reticulon 3; RTN3L: long isoform of RTN3; siRNA: small interfering RNA; SARS: selective autophagy receptors; ss: signal sequence; TEM: transmission electron microscopy, TEX264: testis expressed gene 264; TMT: tandem mass tagging.
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PMID:TEX264 is a major receptor for mammalian reticulophagy. 3100 38