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PreprintCited by 12Ubiquitin and proteasome pathwaysCellular transport and secretionAutophagy in Disease and Therapy

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The Dsc ubiquitin ligase complex identifies transmembrane degrons to degrade orphaned proteins at the Golgi

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Weyer, Yannick, Schwabl, Sinead Iduna, Tang, Xuechen, Widerin, Michael A., Niedrist, Veronika, Tettamanti, Maria G., Weys, Sabine, Sarg, Bettina, Kremser, Leopold, Liedl, Klaus R., Schmidt, Oliver, Teis, David·2024·Nature Communications
DOI 10.1101/2024.03.11.584465PMC PMC11513148

Preprint — published as 10.1038/s41467-024-53676-6

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Abstract

The Golgi apparatus is essential for protein sorting, yet its quality control mechanisms are poorly understood. Here we show that the Dsc ubiquitin ligase complex, particularly the rhomboid pseudo-protease subunit, Dsc2, assesses the hydrophobic length of α-helical transmembrane domains (TMDs) at the Golgi. Thereby the Dsc complex interacts with orphaned ER and Golgi proteins that have shorter TMDs and ubiquitinates them for targeted degradation. Some Dsc substrates will be K63 polyubiquitinated for ESCRT dependent vacuolar degradation or K48 polyubiquitinated for e ndosome and G olgi a ssociated proteasomal d egradation (EGAD). Other Dsc substrates are exclusively extracted by Cdc48 for EGAD. The accumulation of Dsc substrates entails a specific increase in glycerophospholipids with shorter and asymmetric fatty acyl chains. Hence, the Dsc complex mediates the selective degradation of orphaned proteins at the sorting center of cells, which prevents their spreading across other organelles and thus preserves cellular membrane protein and lipid composition.

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Research works printed but not linked: 113

  1. 10.1146/annurev.cellbio.24.110707.175421 · DOI
  2. 10.1016/j.abb.2021.108921 · DOI
  3. 10.1016/j.ceb.2018.03.005 · DOI
  4. 10.1091/mbc.E19-01-0069 · DOI
  5. 10.1038/s41467-019-14038-9 · DOI
  6. 10.15252/embj.201593191 · DOI · Paper page
  7. 10.15252/embj.2018101433 · DOI
  8. 10.1016/j.molcel.2018.07.001 · DOI · Paper page
  9. 10.1016/j.yexcr.2021.112617 · DOI
  10. 10.1016/j.ceb.2022.02.008 · DOI
  11. 10.3390/cells11050780 · DOI
  12. 10.3389/fmolb.2023.1197921 · DOI
  13. 10.1016/j.molcel.2011.02.035 · DOI
  14. 10.1074/mcp.M114.040774 · DOI
  15. 10.7554/eLife.33116 · DOI
  16. 10.1038/ncb743 · DOI
  17. 10.1105/tpc.112.107888 · DOI
  18. 10.1038/sj.embor.7400203 · DOI
  19. 10.1016/j.molcel.2021.05.004 · DOI
  20. 10.15252/embj.2019102679 · DOI
  21. 10.1038/s41580-023-00633-8 · DOI
  22. 10.1101/cshperspect.a041247 · DOI
  23. 10.1038/sj.emboj.7600724 · DOI
  24. 10.1016/j.celrep.2015.08.026 · DOI
  25. 10.1083/jcb.201505062 · DOI
  26. 10.1083/jcb.201902127 · DOI
  27. 10.1016/j.molcel.2022.08.008 · DOI
  28. 10.1074/jbc.RA120.013222 · DOI
  29. 10.15252/embj.2022112275 · DOI
  30. 10.1038/s41586-023-06739-5 · DOI · Paper page
  31. 10.1038/nature11354 · DOI
  32. 10.1002/pmic.200900258 · DOI
  33. 10.1186/1741-7007-7-50 · DOI
  34. 10.1101/2022.04.08.487609 · DOI
  35. 10.1016/j.cell.2010.05.037 · DOI
  36. 10.1016/j.devcel.2016.09.030 · DOI
  37. 10.1016/j.devcel.2012.10.009 · DOI
  38. 10.1038/nature13474 · DOI · Paper page
  39. 10.3389/fcell.2020.00756 · DOI
  40. 10.1016/j.cub.2019.11.043 · DOI
  41. 10.1074/jbc.M306584200 · DOI
  42. 10.1093/nar/gkab1061 · DOI · Paper page
  43. 10.15252/msb.202110207 · DOI
  44. 10.1111/j.1600-0854.2007.00610.x · DOI
  45. 10.1126/science.1245321 · DOI
  46. 10.1016/j.molcel.2017.12.012 · DOI
  47. 10.1074/jbc.M116.770610 · DOI
  48. 10.1091/mbc.E04-10-0873 · DOI
  49. 10.1093/emboj/19.17.4485 · DOI
  50. 10.1074/jbc.M302406200 · DOI
  51. 10.1126/science.aao0076 · DOI
  52. 10.1126/sciadv.abq8303 · DOI
  53. 10.1016/j.celrep.2021.109840 · DOI
  54. 10.1126/science.aaz2449 · DOI
  55. 10.1016/s0092-8674(00)80574-7 · DOI
  56. 10.1128/MCB.00962-10 · DOI
  57. 10.1074/jbc.M110.110551 · DOI
  58. 10.1016/j.cell.2004.11.013 · DOI
  59. 10.1016/j.cell.2007.11.023 · DOI
  60. 10.1111/tra.12485 · DOI
  61. 10.1016/j.tcb.2020.11.011 · DOI
  62. 10.1016/j.molcel.2017.04.024 · DOI
  63. 10.1038/emboj.2010.6 · DOI
  64. 10.1083/jcb.201806094 · DOI
  65. 10.7554/eLife.00173 · DOI
  66. 10.1016/j.molcel.2012.06.008 · DOI
  67. 10.1091/mbc.E17-03-0184 · DOI
  68. 10.1016/j.celrep.2024.113717 · DOI
  69. Carolin Körner , J.-H.S., Bianca M . Esch, Kristian Parey, Stefan Walter, David Teis, Dovile Januliene, Oliver Schmidt, Arne Moeller, Florian Fröhlich (2024). The structure of the Orm2-containing serine palmitoyltransferase complex reveals distinct inhibitory potentials of yeast Orm proteins. bioRxiv. · DOI
  70. 10.1126/science.abm4805 · DOI · Paper page
  71. 10.1016/j.molcel.2019.10.003 · DOI
  72. 10.1038/nature14096 · DOI
  73. 10.1126/science.1255638 · DOI
  74. 10.15252/embr.202254689 · DOI
  75. 10.15252/embr.201745603 · DOI
  76. 10.1016/j.bbamcr.2008.05.008 · DOI
  77. 10.3389/fphys.2015.00089 · DOI
  78. 10.1073/pnas.1404582111 · DOI
  79. 10.1126/science.8362242 · DOI
  80. 10.1038/s41467-017-01328-3 · DOI
  81. 10.1126/sciadv.aba5130 · DOI
  82. 10.1242/jcs.039339 · DOI
  83. 10.1093/emboj/16.8.1832 · DOI
  84. 10.1083/jcb.200710093 · DOI
  85. 10.1242/jcs.202937 · DOI
  86. 10.1242/jcs.130658 · DOI
  87. 10.1016/j.cub.2019.12.010 · DOI
  88. 10.7554/eLife.34394 · DOI
  89. 10.1073/pnas.1019267108 · DOI
  90. 10.1093/genetics/iyac191 · DOI
  91. 10.1038/nature02026 · DOI · Paper page
  92. 10.1016/j.cell.2007.07.036 · DOI · Paper page
  93. 10.1093/nar/gkr703 · DOI
  94. 10.1002/jcc.23702 · DOI
  95. 10.1021/acs.jcim.3c01153 · DOI
  96. 10.1063/1.445869 · DOI
  97. 10.1021/acs.jctc.5b00255 · DOI
  98. 10.1021/acs.jctc.1c01217 · DOI
  99. 10.1016/j.bpj.2017.08.010 · DOI
  100. 10.7554/eLife.64087 · DOI
  101. 10.1021/ct400314y · DOI
  102. 10.1093/bioinformatics/btu037 · DOI
  103. 10.1016/0263-7855(96)00018-5 · DOI · Paper page
  104. 10.1002/1097-0061(20000630)16:9<857::AID-YEA561>3.0.CO;2-B · DOI
  105. 10.1093/biomet/93.3.491 · DOI · Paper page
  106. 10.1128/MCB.8.11.4936 · DOI
  107. 10.1093/emboj/16.8.1820 · DOI
  108. 10.1093/genetics/100.4.547 · DOI
  109. Demarini, D.J., Shah, N.G., Wach, A., Brachat, A., Philippsen, P., and Pringle, J.R, 1998, Additional modules for versatile and economical PCR-based gene deletion and modification in Saccharomyces cerevisiae. Yeast, 14, 953-961
  110. 10.1080/00362178385380431 · DOI
  111. 10.1083/jcb.201310114 · DOI
  112. 10.7554/eLife.07736 · DOI · Paper page
  113. 10.1038/nmeth.2089 · DOI · Paper page

Metadata

Authors
Weyer, Y., Schwabl, S. I., Tang, X., Widerin, M. A., Niedrist, V., Tettamanti, M. G., Weys, S., Sarg, B., Kremser, L., Liedl, K. R., Schmidt, O., & Teis, D.
Affiliations
  • Innsbruck Medical University (AT)
  • Universität Innsbruck (AT)
  • University of Geneva (CH)
Corresponding author
Teis, David
ORCID
Venue
Nature Communications
Publisher
openRxiv
Published
2024-03-12
Volume
15
Issue
1
Pages
9257-9257
ISSN
2041-1723 (ISSN-L)
DOI
10.1101/2024.03.11.584465
PMC
PMC11513148
OpenAlex
W4403784870
Cited by
12
References
1
Citations by year
2026: 7 · 2025: 4 · 2024: 1
FWCI
1.63
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Nature Communications (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Institute of Science and Technology Austria (submittedVersion, cc-by)
  • RePEc: Research Papers in Economics (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • Digital Library of the University of Innsbruck (University of Innsbruck) (submittedVersion, cc-by)
Funders
  • European Commission (HORIZON2020, 847681)
  • Fonds National de la Recherche Luxembourg (13571826)
  • Austrian Science Fund (DOC82, P32161, 10.55776/DOC82, P34907, 10.55776/P36187)
  • Horizon 2020 Framework Programme (847681)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
Keywords
protein degradation, orphan proteins, Cdc48, ESCRT, vacuolar degradation, glycerophospholipids, membrane lipid composition, protein sorting
MeSH terms
Degrons, Endoplasmic Reticulum, Golgi Apparatus, Membrane Proteins, Saccharomyces cerevisiae, Glycerophospholipids, Protein Transport, Saccharomyces cerevisiae Proteins, Ubiquitin-Protein Ligases, Endosomal Sorting Complexes Required for Transport, Proteolysis

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