Academic Journal
A role for CASM in the repair of damaged Golgi architecture.
| Τίτλος: | A role for CASM in the repair of damaged Golgi architecture. |
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| Συγγραφείς: | Oh S; Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, Albuquerque, NM, USA., Ullah S; Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, Albuquerque, NM, USA., Saha B; Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.; Department of Cell and Molecular Biology, Manipal School of Life Sciences, Manipal Academy of Higher Education, Manipal, India., Mandell MA; Department of Molecular Genetics and Microbiology, University of New Mexico Health Sciences Center, Albuquerque, NM, USA.; Autophagy, Inflammation and Metabolism Center of Biomedical Research Excellence, University of New Mexico Health Sciences Center, Albuquerque, NM, USA. |
| Πηγή: | Autophagy [Autophagy] 2026 Sep; Vol. 22 (9), pp. 2268-2286. Date of Electronic Publication: 2026 May 18. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Taylor & Francis Country of Publication: United States NLM ID: 101265188 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1554-8635 (Electronic) Linking ISSN: 15548627 NLM ISO Abbreviation: Autophagy Subsets: MEDLINE |
| Imprint Name(s): | Publication: 2015- : Philadelphia, PA : Taylor & Francis Original Publication: Georgetown, TX : Landes Bioscience, 2005- |
| Ιατρικοί όροι (MeSH): | Golgi Apparatus*/metabolism , Golgi Apparatus*/ultrastructure , Autophagy*/physiology, Microtubule-Associated Proteins/metabolism ; Lysosomes/metabolism ; Humans ; Animals |
| Περίληψη: | The term CASM describes a process in which MAP1LC3B/LC3B and other Atg8-family proteins are covalently ligated to lipids in damaged endomembranes. While CASM is commonly described as a cytoprotective response to multiple types of membrane damage, how CASM helps cells maintain homeostasis is still unclear. Here, we show that CASM maintains Golgi apparatus architecture following the loss of TRIM46, a ubiquitin ligase with roles in microtubule organization. TRIM46 deficient cells were notable for enhanced TFEB-driven lysosomal biogenesis and Golgi ribbon fragmentation, with colocalization of the trans-Golgi marker TGOLN2 and the Atg8-family proteins LC3B and GABARAP. Further studies revealed that the Golgi Atg8ylation seen in TRIM46 knockout cells was not degradative and mechanistically resembled CASM. Genetic inhibition of CASM in TRIM46 deficient cells reduced TFEB activation and exacerbated the Golgi morphology defects, suggesting that CASM contributes to Golgi repair. Accordingly, Golgi reformation after drug-induced fragmentation was impaired upon knockdown of CASM genes. Together, these studies identify lysosomal biogenesis and CASM as coordinated features of a Golgi damage response, with CASM acting to preserve Golgi integrity.Abbreviations: AMPK (AMP-activated protein kinase); ATG3 (autophagy related 3); ATG5 (autophagy related 5); ATG7 (autophagy related 7); ATG12 (autophagy related 12); ATG13 (autophagy related 13); ATG16L1 (autophagy related 16 like 1); BECN1 (beclin 1); CASM, conjugation of Atg8 to single membranes; GABARAP (GABA type A receptor-associated protein); GABARAPL1 (GABA type A receptor associated protein like 1); GABARAPL2 (GABA type A receptor associated protein like 2); GOLGA2 (golgin A2); HT (HaloTag); HL (HaloTag ligand); MAP1LC3A/LC3A (microtubule associated protein 1 light chain 3 alpha); MAP1LC3B/LC3B (microtubule associated protein 1 light chain 3 beta); MAP1LC3C/LC3C (microtubule associated protein 1 light chain 3 gamma); MTORC1 (mechanistic target of rapamycin kinase complex 1); PE (phosphatidylethanolamine); PIK3C3/VPS34 (phosphatidylinositol 3-kinase catalytic subunit type 3); PS (phosphatidylserine); TECPR1 (tectonin beta-propellor repeat containing 1); SQSTM1/p62 (sequestosome 1); TFEB (transcription factor EB); TFE3 (transcription factor binding to IGHM enhancer 3); TGOLN2 (trans-golgi network protein 2); TRIM46 (tripartite motif containing 46); ULK1 (unc-51 like autophagy activating kinase 1); ULK2 (unc-51 like autophagy activating kinase 2): VAIL (V-ATPase-ATG16L1 induced LC3 lipidation). |
| Σχόλια: | Update of: bioRxiv. 2025 Sep 04:2025.09.04.674289. doi: 10.1101/2025.09.04.674289.. (PMID: 40950167) |
| References: | Cell Death Dis. 2016 Aug 11;7(8):e2330. (PMID: 27512951) J Cell Biol. 2022 Jul 4;221(7):. (PMID: 35699692) EMBO J. 2023 Sep 4;42(17):e113012. (PMID: 37409490) J Cell Biol. 2023 Dec 4;222(12):. (PMID: 37796195) Science. 2011 Jun 17;332(6036):1429-33. (PMID: 21617040) J Cell Sci. 2024 Aug 1;137(15):. (PMID: 39145464) Sci Adv. 2022 Oct 28;8(43):eabo1274. (PMID: 36288315) Cell. 2014 Jan 30;156(3):413-27. (PMID: 24485452) Nat Struct Mol Biol. 2022 Jan;29(1):67-77. (PMID: 35046574) Nat Cell Biol. 2011 Oct 16;13(11):1335-43. (PMID: 22002674) Autophagy. 2021 Dec;17(12):3957-3975. (PMID: 33734022) J Mol Biol. 2020 Jan 3;432(1):231-239. (PMID: 31449799) Nat Cell Biol. 2009 Sep;11(9):1069-80. (PMID: 19701196) Sci Adv. 2021 Oct;7(40):eabj2485. (PMID: 34597140) EMBO Rep. 2022 Aug 3;23(8):e55192. (PMID: 35758175) Science. 2009 Jul 24;325(5939):473-7. (PMID: 19556463) Sci Signal. 2012 Jun 12;5(228):ra42. (PMID: 22692423) Sci Adv. 2025 Mar 28;11(13):eadt3311. (PMID: 40138395) Cell Death Differ. 2019 Aug;26(8):1467-1484. (PMID: 30349077) J Mol Biol. 2024 Aug 1;436(15):168532. (PMID: 38479594) PLoS Pathog. 2024 Dec 9;20(12):e1012748. (PMID: 39652582) EMBO Rep. 2020 Mar 4;21(3):e48385. (PMID: 31984633) Autophagy. 2015;11(1):88-99. (PMID: 25484071) EMBO J. 2012 Mar 7;31(5):1095-108. (PMID: 22343943) PLoS Pathog. 2018 Feb 1;14(2):e1006787. (PMID: 29389992) Science. 2011 Nov 4;334(6056):678-83. (PMID: 22053050) Cell Death Differ. 2020 Mar;27(3):887-902. (PMID: 31969691) Nat Rev Mol Cell Biol. 2020 Apr;21(4):183-203. (PMID: 31937935) Mol Cell. 2024 Oct 17;84(20):3979-3996.e9. (PMID: 39423796) EMBO J. 2023 Sep 4;42(17):e113105. (PMID: 37409525) Mol Cell. 2021 May 6;81(9):2031-2040.e8. (PMID: 33909989) Cell. 2019 Jul 25;178(3):552-566.e20. (PMID: 31327526) Proc Natl Acad Sci U S A. 2017 Apr 25;114(17):E3462-E3471. (PMID: 28389568) J Mol Biol. 2025 Sep 15;437(18):169138. (PMID: 40221132) Autophagy. 2016;12(1):1-222. (PMID: 26799652) Elife. 2022 Aug 08;11:. (PMID: 35938926) Autophagy. 2012 Jun;8(6):903-14. (PMID: 22576015) Nature. 2016 Jun 15;534(7608):553-7. (PMID: 27309807) J Biol Chem. 2018 Apr 13;293(15):5404-5413. (PMID: 29187595) EMBO J. 2024 Jul;43(14):2954-2978. (PMID: 38822137) Trends Biochem Sci. 2017 Apr;42(4):297-311. (PMID: 28118948) Dev Cell. 2014 Aug 25;30(4):394-409. (PMID: 25127057) Front Neurosci. 2023 Feb 16;17:1120086. (PMID: 36875643) J Cell Biol. 2021 Jun 7;220(6):. (PMID: 33871553) Autophagy. 2007 Sep-Oct;3(5):452-60. (PMID: 17534139) EMBO Rep. 2023 Sep 6;24(9):e56841. (PMID: 37381828) Elife. 2013 Aug 06;2:e00947. (PMID: 23930225) J Cell Biol. 2020 Dec 7;219(12):. (PMID: 33201170) Nat Rev Mol Cell Biol. 2023 Mar;24(3):167-185. (PMID: 36302887) Dev Cell. 2025 Nov 3;60(21):2862-2879.e8. (PMID: 40609542) Mol Biol Cell. 2007 Mar;18(3):1073-82. (PMID: 17215520) EMBO J. 2021 Apr 1;40(7):e106922. (PMID: 33644904) Nat Rev Genet. 2023 Jun;24(6):382-400. (PMID: 36635405) Neuron. 2015 Dec 16;88(6):1208-1226. (PMID: 26671463) Proc Natl Acad Sci U S A. 2014 Apr 1;111(13):E1230-9. (PMID: 24639524) J Cell Sci. 2018 Feb 8;131(3):. (PMID: 29361552) Front Pharmacol. 2020 Mar 11;11:308. (PMID: 32226386) Mol Cell. 2024 Aug 8;84(15):2966-2983.e9. (PMID: 39089251) Nature. 2023 Nov;623(7985):167-174. (PMID: 37757899) J Cell Sci. 2024 Feb 1;137(3):. (PMID: 38329417) Annu Rev Virol. 2018 Sep 29;5(1):385-405. (PMID: 29949725) Methods Enzymol. 2017;587:43-54. (PMID: 28253971) Nat Commun. 2022 Aug 10;13(1):4685. (PMID: 35948564) EMBO J. 2024 Nov;43(21):5085-5113. (PMID: 39284911) J Cell Biol. 2022 Jun 6;221(6):. (PMID: 35511089) Cell Death Differ. 2019 Sep;26(9):1735-1749. (PMID: 30568238) |
| Grant Information: | P20 GM121176 United States GM NIGMS NIH HHS; P30 CA118100 United States CA NCI NIH HHS; R01 AI155746 United States AI NIAID NIH HHS; T32 AI007538 United States AI NIAID NIH HHS |
| Contributed Indexing: | Keywords: Atg8ylation; CASM; VAIL; autophagy; golgi damage/golgi fragmentation; lysosomal biogenesis; tripartite motif |
| Substance Nomenclature: | 0 (Microtubule-Associated Proteins) |
| Entry Date(s): | Date Created: 20260512 Date Completed: 20260821 Latest Revision: 20260922 |
| Update Code: | 20260922 |
| PubMed Central ID: | PMC13217580 |
| DOI: | 10.1080/15548627.2026.2673560 |
| PMID: | 42115886 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1554-8635 |
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| DOI: | 10.1080/15548627.2026.2673560 |