1932

Abstract

Numerous trafficking and quality control pathways evolved to handle the diversity of proteins made by eukaryotic cells. However, at every step along the biosynthetic pathway, there is the potential for quality control system failure. This review focuses on the mechanisms of disrupted proteostasis. Inspired by diseases caused by misfolded proteins in the kidney (mucin 1 and uromodulin), we outline the general principles of protein biosynthesis, delineate the recognition and degradation pathways targeting misfolded proteins, and discuss the role of cargo receptors in protein trafficking and lipid homeostasis. We also discuss technical approaches including live-cell fluorescent microscopy, chemical screens to elucidate trafficking mechanisms, multiplexed single-cell CRISPR screening platforms to systematically delineate mechanisms of proteostasis, and the advancement of novel tools to degrade secretory and membrane-associated proteins. By focusing on components of trafficking that go awry, we highlight ongoing efforts to understand fundamental mechanisms of disrupted proteostasis and implications for the treatment of human proteinopathies.

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2023-02-10
2024-04-21
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Literature Cited

  1. 1.
    Balch WE, Morimoto RI, Dillin A, Kelly JW. 2008. Adapting proteostasis for disease intervention. Science 319:5865916–19
    [Google Scholar]
  2. 2.
    Uhlén M, Fagerberg L, Hallström BM, Lindskog C, Oksvold P et al. 2015. Tissue-based map of the human proteome. Science 347:62201260419
    [Google Scholar]
  3. 3.
    Lord JM, Roberts LM, Stirling CJ. 2005. Quality control: another player joins the ERAD cast. Curr. Biol. 15:23R963–64
    [Google Scholar]
  4. 4.
    Meusser B, Hirsch C, Jarosch E, Sommer T 2005. ERAD: the long road to destruction. Nat. Cell Biol. 7:8766–72
    [Google Scholar]
  5. 5.
    Woodman PG. 2003. p97, a protein coping with multiple identities. J. Cell Sci. 116:Part 214283–90
    [Google Scholar]
  6. 6.
    Deak PM, Wolf DH. 2001. Membrane topology and function of Der3/Hrd1p as a ubiquitin-protein ligase (E3) involved in endoplasmic reticulum degradation. J. Biol. Chem. 276:1410663–69
    [Google Scholar]
  7. 7.
    Neal S, Ohtake F, Cuervo AM, Hegde RS, Jakob U et al. 2022. Quality control: maintaining molecular order and preventing cellular chaos. Mol. Cell 82:81390–97
    [Google Scholar]
  8. 8.
    Bedford L, Lowe J, Dick LR, Mayer RJ, Brownell JE. 2010. Ubiquitin-like protein conjugation and the ubiquitin-proteasome system as drug targets. Nat. Rev. Drug Discov. 10:129–46
    [Google Scholar]
  9. 9.
    Lemberg MK, Strisovsky K. 2021. Maintenance of organellar protein homeostasis by ER-associated degradation and related mechanisms. Mol. Cell 81:122507–19
    [Google Scholar]
  10. 10.
    Connell P, Ballinger CA, Jiang J, Wu Y, Thompson LJ et al. 2001. The co-chaperone CHIP regulates protein triage decisions mediated by heat-shock proteins. Nat. Cell Biol. 3:193–96
    [Google Scholar]
  11. 11.
    Meacham GC, Patterson C, Zhang W, Younger JM, Cyr DM. 2001. The Hsc70 co-chaperone CHIP targets immature CFTR for proteasomal degradation. Nat. Cell Biol. 3:1100–5
    [Google Scholar]
  12. 12.
    Yamamoto A, Friedlein A, Imai Y, Takahashi R, Kahle PJ, Haass C. 2005. Parkin phosphorylation and modulation of its E3 ubiquitin ligase activity. J. Biol. Chem. 280:53390–99
    [Google Scholar]
  13. 13.
    Imai Y, Soda M, Inoue H, Hattori N, Mizuno Y, Takahashi R. 2001. An unfolded putative transmembrane polypeptide, which can lead to endoplasmic reticulum stress, is a substrate of Parkin. Cell 105:7891–902
    [Google Scholar]
  14. 14.
    Palade G. 1975. Intracellular aspects of the process of protein synthesis. Science 189:4200347–58
    [Google Scholar]
  15. 15.
    Lee MCS, Miller EA, Goldberg J, Orci L, Schekman R. 2004. Bi-directional protein transport between the ER and Golgi. Annu. Rev. Cell Dev. Biol. 20:87–123
    [Google Scholar]
  16. 16.
    Yan R, Chen K, Wang B, Xu K 2022. SURF4-induced tubular ERGIC selectively expedites ER-to-Golgi transport. Dev. Cell 57:4512–25.e8
    [Google Scholar]
  17. 17.
    Cybulsky AV. 2010. Endoplasmic reticulum stress in proteinuric kidney disease. Kidney Int 77:3187–93
    [Google Scholar]
  18. 18.
    Cybulsky AV. 2017. Endoplasmic reticulum stress, the unfolded protein response and autophagy in kidney diseases. Nat. Rev. Nephrol. 13:11681–96
    [Google Scholar]
  19. 19.
    Araki K, Nagata K. 2012. Protein folding and quality control in the ER. Cold Spring Harb. Perspect. Biol. 4:8a015438
    [Google Scholar]
  20. 20.
    Brodsky JL, Skach WR. 2011. Protein folding and quality control in the endoplasmic reticulum: recent lessons from yeast and mammalian cell systems. Curr. Opin. Cell Biol. 23:4464–75
    [Google Scholar]
  21. 21.
    Brandizzi F, Barlowe C. 2013. Organization of the ER-Golgi interface for membrane traffic control. Nat. Rev. Mol. Cell Biol. 14:6382–92
    [Google Scholar]
  22. 22.
    Beck R, Adolf F, Weimer C, Bruegger B, Wieland FT 2009. ArfGAP1 activity and COPI vesicle biogenesis. Traffic 10:3307–15
    [Google Scholar]
  23. 23.
    Adolf F, Rhiel M, Hessling B, Gao Q, Hellwig A et al. 2019. Proteomic profiling of mammalian COPII and COPI vesicles. Cell Rep 26:1250–65.e5
    [Google Scholar]
  24. 24.
    Weigel AV, Chang C-L, Shtengel G, Xu CS, Hoffman DP et al. 2021. ER-to-Golgi protein delivery through an interwoven, tubular network extending from ER. Cell 184:92412–29.e16
    [Google Scholar]
  25. 25.
    Popoff V, Adolf F, Brügger B, Wieland F 2011. COPI budding within the Golgi stack. Cold Spring Harb. Perspect. Biol. 3:a005231
    [Google Scholar]
  26. 26.
    Ward TH, Polishchuk RS, Caplan S, Hirschberg K, Lippincott-Schwartz J. 2001. Maintenance of Golgi structure and function depends on the integrity of ER export. J. Cell Biol. 155:4557–70
    [Google Scholar]
  27. 27.
    Emmer BT, Hesketh GG, Kotnik E, Tang VT, Lascuna PJ et al. 2018. The cargo receptor SURF4 promotes the efficient cellular secretion of PCSK9. eLife 7:e38839
    [Google Scholar]
  28. 28.
    Strating JRPM, Martens GJM. 2009. The p24 family and selective transport processes at the ER-Golgi interface. Biol. Cell 101:9495–509
    [Google Scholar]
  29. 29.
    Belden WJ, Barlowe C. 2001. Distinct roles for the cytoplasmic tail sequences of Emp24p and Erv25p in transport between the endoplasmic reticulum and Golgi complex. J. Biol. Chem. 276:4643040–48
    [Google Scholar]
  30. 30.
    Gomez-Navarro N, Miller E. 2016. Protein sorting at the ER-Golgi interface. J. Cell Biol. 215:6769–78
    [Google Scholar]
  31. 31.
    Dvela-Levitt M, Kost-Alimova M, Emani M, Kohnert E, Thompson R et al. 2019. Small molecule targets TMED9 and promotes lysosomal degradation to reverse proteinopathy. Cell 178:3521–35.e23
    [Google Scholar]
  32. 32.
    Li S, Yan R, Xu J, Zhao S, Ma X et al. 2021. A new type of ERGIC-ERES membrane contact mediated by TMED9 and SEC12 is required for autophagosome biogenesis. Cell Res. 32:2119–38
    [Google Scholar]
  33. 33.
    Karanasios E, Walker SA, Okkenhaug H, Manifava M, Hummel E et al. 2016. Autophagy initiation by ULK complex assembly on ER tubulovesicular regions marked by ATG9 vesicles. Nat. Commun. 7:12420
    [Google Scholar]
  34. 34.
    Goldberg J, Mancias JD. 2008. Crystal structure of the mammalian COPII-coat protein Sec23a/24a complexed with the SNARE protein Sec22 and bound to the transport signal sequence of vesicular stomatitis virus glycoprotein. EMBO J. 27:2918–28
    [Google Scholar]
  35. 35.
    Mossessova E, Bickford LC, Goldberg J. 2003. Crystal structure of the COPII coat subunit, Sec24, complexed with a peptide from the SNARE protein Bet1. Cell 114:483–95
    [Google Scholar]
  36. 36.
    Miller EA, Beilharz TH, Malkus PN, Lee MCS, Hamamoto S et al. 2003. Multiple cargo binding sites on the COPII subunit Sec24p ensure capture of diverse membrane proteins into transport vesicles. Cell 114:4497–509
    [Google Scholar]
  37. 37.
    Gomez-Navarro N, Maldutyte J, Poljak K, Peak-Chew S-Y, Orme J et al. 2022. Selective inhibition of protein secretion by abrogating receptor–coat interactions during ER export. PNAS 119:31e2202080119
    [Google Scholar]
  38. 38.
    Khoriaty R, Vasievich MP, Ginsburg D. 2012. The COPII pathway and hematologic disease. Blood 120:131–38
    [Google Scholar]
  39. 39.
    Dell'Angelica EC, Bonifacino JS 2019. Coatopathies: genetic disorders of protein coats. Annu. Rev. Cell Dev. Biol. 35:131–68
    [Google Scholar]
  40. 40.
    Routledge KE, Gupta V, Balch WE. 2010. Emergent properties of proteostasis-COPII coupled systems in human health and disease. Mol. Membr. Biol. 27:8385–97
    [Google Scholar]
  41. 41.
    Park J-S, Ji IJ, An HJ, Kang M-J, Kang S-W et al. 2015. Disease-associated mutations of TREM2 alter the processing of N-linked oligosaccharides in the Golgi apparatus. Traffic 16:5510–18
    [Google Scholar]
  42. 42.
    Kleinberger G, Yamanishi Y, Suárez-Calvet M, Czirr E, Lohmann E et al. 2014. TREM2 mutations implicated in neurodegeneration impair cell surface transport and phagocytosis. Sci. Transl. Med. 6:243243ra86
    [Google Scholar]
  43. 43.
    Deczkowska A, Weiner A, Amit I. 2020. The physiology, pathology, and potential therapeutic applications of the TREM2 signaling pathway. Cell 181:61207–17
    [Google Scholar]
  44. 44.
    Wang Y, Cella M, Mallinson K, Ulrich JD, Young KL et al. 2015. TREM2 lipid sensing sustains the microglial response in an Alzheimer's disease model. Cell 160:61061–71
    [Google Scholar]
  45. 45.
    Cooper AA, Gitler AD, Cashikar A, Haynes CM, Hill KJ et al. 2006. α-Synuclein blocks ER-Golgi traffic and Rab1 rescues neuron loss in Parkinson's models. Science 313:5785324–28
    [Google Scholar]
  46. 46.
    Fromme JC, Ravazzola M, Hamamoto S, Al-Balwi M, Eyaid W et al. 2007. The genetic basis of a craniofacial disease provides insight into COPII coat assembly. Dev. Cell 13:5623–34
    [Google Scholar]
  47. 47.
    Deng Z, Chong Z, Law CS, Mukai K, Ho FO et al. 2020. A defect in COPI-mediated transport of STING causes immune dysregulation in COPA syndrome. J. Exp. Med. 217:11e20201045
    [Google Scholar]
  48. 48.
    Walter P, Ron D 2011. The unfolded protein response: from stress pathway to homeostatic regulation. Science 334:60591081–86
    [Google Scholar]
  49. 49.
    Iwawaki T, Akai R, Kohno K, Miura M. 2004. A transgenic mouse model for monitoring endoplasmic reticulum stress. Nat. Med. 10:198–102
    [Google Scholar]
  50. 50.
    Mao C, Tai W-C, Bai Y, Poizat C, Lee AS. 2006. In vivo regulation of Grp78/BiP transcription in the embryonic heart: role of the endoplasmic reticulum stress response element and GATA-4. J. Biol. Chem. 281:138877–87
    [Google Scholar]
  51. 51.
    Adamson B, Norman TM, Jost M, Cho MY, Nuñez JK et al. 2016. A multiplexed single-cell CRISPR screening platform enables systematic dissection of the unfolded protein response. Cell 167:71867–82.e21
    [Google Scholar]
  52. 52.
    Macosko EZ, Basu A, Satija R, Nemesh J, Shekhar K et al. 2015. Highly parallel genome-wide expression profiling of individual cells using nanoliter droplets. Cell 161:51202–14
    [Google Scholar]
  53. 53.
    Klein AM, Mazutis L, Akartuna I, Tallapragada N, Veres A et al. 2015. Droplet barcoding for single-cell transcriptomics applied to embryonic stem cells. Cell 161:51187–201
    [Google Scholar]
  54. 54.
    Zheng GXY, Terry JM, Belgrader P, Ryvkin P, Bent ZW et al. 2017. Massively parallel digital transcriptional profiling of single cells. Nat. Commun. 8:14049
    [Google Scholar]
  55. 55.
    Gilbert LA, Larson MH, Morsut L, Liu Z, Brar GA et al. 2013. CRISPR-mediated modular RNA-guided regulation of transcription in eukaryotes. Cell 154:2442–51
    [Google Scholar]
  56. 56.
    Schaeffer C, Creatore A, Rampoldi L. 2014. Protein trafficking defects in inherited kidney diseases. Nephrol. Dial. Transplant. 29:Suppl. 4iv33–44
    [Google Scholar]
  57. 57.
    Vivante A, Hildebrandt F. 2016. Exploring the genetic basis of early-onset chronic kidney disease. Nat. Rev. Nephrol. 12:3133–46
    [Google Scholar]
  58. 58.
    Pavenstädt H, Kriz W, Kretzler M. 2003. Cell biology of the glomerular podocyte. Physiol. Rev. 83:1253–307
    [Google Scholar]
  59. 59.
    Kaufman DR, Papillon J, Larose L, Iwawaki T, Cybulsky AV. 2017. Deletion of inositol-requiring enzyme-1α in podocytes disrupts glomerular capillary integrity and autophagy. Mol. Biol. Cell 28:121636–51
    [Google Scholar]
  60. 60.
    Drozdova T, Papillon J, Cybulsky AV. 2013. Nephrin missense mutations: induction of endoplasmic reticulum stress and cell surface rescue by reduction in chaperone interactions. Physiol. Rep. 1:4e00086
    [Google Scholar]
  61. 61.
    Pieri M, Stefanou C, Zaravinos A, Erguler K, Stylianou K et al. 2014. Evidence for activation of the unfolded protein response in collagen IV nephropathies. J. Am. Soc. Nephrol. 25:2260–75
    [Google Scholar]
  62. 62.
    The UniProt Consortium 2017. UniProt: the universal protein knowledgebase. Nucleic Acids Res. 45:D1D158–69
    [Google Scholar]
  63. 63.
    Hessa T, Sharma A, Mariappan M, Eshleman HD, Gutierrez E, Hegde RS. 2011. Protein targeting and degradation are coupled for elimination of mislocalized proteins. Nature 475:7356394–97
    [Google Scholar]
  64. 64.
    Sikorska N, Lemus L, Aguilera-Romero A, Manzano-Lopez J, Riezman H et al. 2016. Limited ER quality control for GPI-anchored proteins. J. Cell Biol. 213:6693–704
    [Google Scholar]
  65. 65.
    Zavodszky E, Hegde RS. 2019. Misfolded GPI-anchored proteins are escorted through the secretory pathway by ER-derived factors. eLife 8:e46740
    [Google Scholar]
  66. 66.
    Devuyst O, Olinger E, Rampoldi L. 2017. Uromodulin: from physiology to rare and complex kidney disorders. Nat. Rev. Nephrol. 13:9525–44
    [Google Scholar]
  67. 67.
    Devuyst O, Olinger E, Weber S, Eckardt K-U, Kmoch S et al. 2019. Autosomal dominant tubulointerstitial kidney disease. Nat. Rev. Dis. Primers 5:160
    [Google Scholar]
  68. 68.
    Köttgen A, Glazer NL, Dehghan A, Hwang S-J, Katz R et al. 2009. Multiple loci associated with indices of renal function and chronic kidney disease. Nat. Genet. 41:6712–17
    [Google Scholar]
  69. 69.
    Satpute-Krishnan P, Ajinkya M, Bhat S, Itakura E, Hegde RS, Lippincott-Schwartz J. 2014. ER stress-induced clearance of misfolded GPI-anchored proteins via the secretory pathway. Cell 158:3522–33
    [Google Scholar]
  70. 70.
    Dugger BN, Dickson DW. 2017. Pathology of neurodegenerative diseases. Cold Spring Harb. Perspect. Biol. 9:7a028035
    [Google Scholar]
  71. 71.
    Dvela-Levitt M, Shaw JL, Greka A. 2021. A rare kidney disease to cure them all? Towards mechanism-based therapies for proteinopathies. Trends Mol. Med. 27:4394–409
    [Google Scholar]
  72. 72.
    Higuchi-Sanabria R, Frankino PA, Paul JW 3rd, Tronnes SU, Dillin A. 2018. A futile battle? Protein quality control and the stress of aging. Dev. Cell 44:2139–63
    [Google Scholar]
  73. 73.
    Kirby A, Gnirke A, Jaffe DB, Barešová V, Pochet N et al. 2013. Mutations causing medullary cystic kidney disease type 1 lie in a large VNTR in MUC1 missed by massively parallel sequencing. Nat. Genet. 45:3299–303
    [Google Scholar]
  74. 74.
    Pastor-Cantizano N, Montesinos JC, Bernat-Silvestre C, Marcote MJ, Aniento F. 2016. p24 family proteins: key players in the regulation of trafficking along the secretory pathway. Protoplasma 253:4967–85
    [Google Scholar]
  75. 75.
    Thomas G, Horwich A. 2019. Chemical strike against a dominant-inherited MUC1-frameshifted protein associated with progressive kidney disease. Trends Mol. Med. 25:10821–23
    [Google Scholar]
  76. 76.
    Cuervo AM, Stefanis L, Fredenburg R, Lansbury PT, Sulzer D. 2004. Impaired degradation of mutant α-synuclein by chaperone-mediated autophagy. Science 305:56881292–95
    [Google Scholar]
  77. 77.
    Kaushik S, Cuervo AM. 2018. The coming of age of chaperone-mediated autophagy. Nat. Rev. Mol. Cell Biol. 19:6365–81
    [Google Scholar]
  78. 78.
    Bourdenx M, Martín-Segura A, Scrivo A, Rodriguez-Navarro JA, Kaushik S et al. 2021. Chaperone-mediated autophagy prevents collapse of the neuronal metastable proteome. Cell 184:102696–2714.e25
    [Google Scholar]
  79. 79.
    Park C, Suh Y, Cuervo AM. 2015. Regulated degradation of Chk1 by chaperone-mediated autophagy in response to DNA damage. Nat. Commun. 6:6823
    [Google Scholar]
  80. 80.
    Gough NR, Hatem CL, Fambrough DM. 1995. The family of LAMP-2 proteins arises by alternative splicing from a single gene: characterization of the avian LAMP-2 gene and identification of mammalian homologs of LAMP-2b and LAMP-2c. DNA Cell Biol 14:10863–67
    [Google Scholar]
  81. 81.
    Cuervo AM, Dice JF. 2000. Unique properties of lamp2a compared to other lamp2 isoforms. J. Cell Sci. 113:Part 244441–50
    [Google Scholar]
  82. 82.
    Caballero B, Wang Y, Diaz A, Tasset I, Juste YR et al. 2018. Interplay of pathogenic forms of human tau with different autophagic pathways. Aging Cell 17:1e12692
    [Google Scholar]
  83. 83.
    Vekrellis K, Xilouri M, Emmanouilidou E, Rideout HJ, Stefanis L. 2011. Pathological roles of α-synuclein in neurological disorders. Lancet Neurol 10:111015–25
    [Google Scholar]
  84. 84.
    Cuervo AM, Dice JF. 1996. A receptor for the selective uptake and degradation of proteins by lysosomes. Science 273:5274501–3
    [Google Scholar]
  85. 85.
    Napolitano G, Johnson JL, He J, Rocca CJ, Monfregola J et al. 2015. Impairment of chaperone-mediated autophagy leads to selective lysosomal degradation defects in the lysosomal storage disease cystinosis. EMBO Mol. Med. 7:2158–74
    [Google Scholar]
  86. 86.
    Eriksson I, Wäster P, Öllinger K. 2020. Restoration of lysosomal function after damage is accompanied by recycling of lysosomal membrane proteins. Cell Death Dis 11:5370
    [Google Scholar]
  87. 87.
    Dong S, Aguirre-Hernandez C, Scrivo A, Eliscovich C, Arias E et al. 2020. Monitoring spatiotemporal changes in chaperone-mediated autophagy in vivo. Nat. Commun. 11:645
    [Google Scholar]
  88. 88.
    Winter GE, Buckley DL, Paulk J, Roberts JM, Souza A et al. 2015. Phthalimide conjugation as a strategy for in vivo target protein degradation. Science 348:62411376–81
    [Google Scholar]
  89. 89.
    Paiva S-L, Crews CM. 2019. Targeted protein degradation: elements of PROTAC design. Curr. Opin. Chem. Biol. 50:111–19
    [Google Scholar]
  90. 90.
    Banik SM, Pedram K, Wisnovsky S, Ahn G, Riley NM, Bertozzi CR. 2020. Lysosome-targeting chimaeras for degradation of extracellular proteins. Nature 584:7820291–97
    [Google Scholar]
  91. 91.
    O'Reilly MK, Tian H, Paulson JC. 2011. CD22 is a recycling receptor that can shuttle cargo between the cell surface and endosomal compartments of B cells. J. Immunol. 186:31554–63
    [Google Scholar]
  92. 92.
    Azad AK, Rajaram MVS, Schlesinger LS. 2014. Exploitation of the macrophage mannose receptor (CD206) in infectious disease diagnostics and therapeutics. J. Cytol. Mol. Biol. 1:11000003
    [Google Scholar]
  93. 93.
    Ahn G, Banik SM, Miller CL, Riley NM, Cochran JR, Bertozzi CR. 2021. LYTACs that engage the asialoglycoprotein receptor for targeted protein degradation. Nat. Chem. Biol. 17:9937–46
    [Google Scholar]
  94. 94.
    Contreras F-X, Ernst AM, Haberkant P, Björkholm P, Lindahl E et al. 2012. Molecular recognition of a single sphingolipid species by a protein's transmembrane domain. Nature 481:7382525–29
    [Google Scholar]
  95. 95.
    Jiménez-Rojo N, Leonetti MD, Zoni V, Colom A, Feng S et al. Conserved function of ether lipids and sphingolipids in the early secretory pathway. Curr. Biol. 30:193775–87.e7
    [Google Scholar]
  96. 96.
    Wang B, Shen Y, Zhai L, Xia X, Gu H-M et al. 2021. Atherosclerosis-associated hepatic secretion of VLDL but not PCSK9 is dependent on cargo receptor protein Surf4. J. Lipid Res. 62:100091
    [Google Scholar]
  97. 97.
    Wang X, Wang H, Xu B, Huang D, Nie C et al. 2021. Receptor-mediated ER export of lipoproteins controls lipid homeostasis in mice and humans. Cell Metab 33:2350–66.e7
    [Google Scholar]
  98. 98.
    Brown MS, Goldstein JL. 1986. A receptor-mediated pathway for cholesterol homeostasis. Science 232:474634–47
    [Google Scholar]
  99. 99.
    Malkus P, Jiang F, Schekman R. 2002. Concentrative sorting of secretory cargo proteins into COPII-coated vesicles. J. Cell Biol. 159:6915–21
    [Google Scholar]
  100. 100.
    Nie C, Wang H, Wang R, Ginsburg D, Chen X-W. 2018. Dimeric sorting code for concentrative cargo selection by the COPII coat. PNAS 115:14E3155–62
    [Google Scholar]
  101. 101.
    Lam SS, Martell JD, Kamer KJ, Deerinck TJ, Ellisman MH et al. 2015. Directed evolution of APEX2 for electron microscopy and proximity labeling. Nat. Methods 12:151–54
    [Google Scholar]
  102. 102.
    Branon TC, Bosch JA, Sanchez AD, Udeshi ND, Svinkina T et al. 2018. Efficient proximity labeling in living cells and organisms with TurboID. Nat. Biotechnol. 36:9880–87
    [Google Scholar]
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