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Review
. 2019 Dec;76(24):4829-4848.
doi: 10.1007/s00018-019-03246-7. Epub 2019 Jul 30.

Post-translational Modification and Protein Sorting to Small Extracellular Vesicles Including Exosomes by Ubiquitin and UBLs

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Review

Post-translational Modification and Protein Sorting to Small Extracellular Vesicles Including Exosomes by Ubiquitin and UBLs

Hiroshi Ageta et al. Cell Mol Life Sci. .

Abstract

Exosomes, a type of small extracellular vesicles (sEVs), are secreted membrane vesicles that are derived from various cell types, including cancer cells, mesenchymal stem cells, and immune cells via multivesicular bodies (MVBs). These sEVs contain RNAs (mRNA, miRNA, lncRNA, and rRNA), lipids, DNA, proteins, and metabolites, all of which mediate cell-to-cell communication. This communication is known to be implicated in a diverse set of diseases such as cancers and their metastases and degenerative diseases. The molecular mechanisms, by which proteins are modified and sorted to sEVs, are not fully understood. Various cellular processes, including degradation, transcription, DNA repair, cell cycle, signal transduction, and autophagy, are known to be associated with ubiquitin and ubiquitin-like proteins (UBLs). Recent studies have revealed that ubiquitin and UBLs also regulate MVBs and protein sorting to sEVs. Ubiquitin-like 3 (UBL3)/membrane-anchored Ub-fold protein (MUB) acts as a post-translational modification (PTM) factor to regulate efficient protein sorting to sEVs. In this review, we focus on the mechanism of PTM by ubiquitin and UBLs and the pathway of protein sorting into sEVs and discuss the potential biological significance of these processes.

Keywords: Exosome; Multivesicular body; Post-translational modification; Small extracellular vesicle; Ubiquitin; Ubiquitin-like protein.

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References

    1. Traffic. 2009 Oct;10(10):1518-27 - PubMed

References

    1. J Immunol. 2000 Nov 15;165(10):5487-94 - PubMed

References

    1. Immunity. 2006 Dec;25(6):885-94 - PubMed

References

    1. Nat Rev Mol Cell Biol. 2005 Aug;6(8):599-609 - PubMed

References

    1. Brain. 2016 Dec;139(Pt 12):3187-3201 - PubMed

References

    1. FEBS Lett. 1993 Oct 25;333(1-2):169-74 - PubMed

References

    1. Mol Cell Biol. 2000 Nov;20(22):8526-35 - PubMed

References

    1. Proc Natl Acad Sci U S A. 2001 Dec 4;98(25):14440-5 - PubMed

References

    1. EMBO J. 2015 May 12;34(10):1385-98 - PubMed

References

    1. Proc Natl Acad Sci U S A. 2001 Sep 25;98(20):11199-204 - PubMed

References

    1. Cold Spring Harb Perspect Biol. 2010 Feb;2(2):a001057 - PubMed

References

    1. Dev Cell. 2011 Jul 19;21(1):77-91 - PubMed

References

    1. Biochim Biophys Acta. 2007 Jul;1773(7):1116-23 - PubMed

References

    1. Nat Commun. 2016 Aug 23;7:12580 - PubMed

References

    1. J Biol Chem. 1997 Nov 7;272(45):28557-62 - PubMed

References

    1. Nat Cell Biol. 2010 Jan;12(1):19-30; sup pp 1-13 - PubMed

References

    1. Science. 1999 Sep 10;285(5434):1737-41 - PubMed

References

    1. Rev Neurosci. 2017 Nov 27;28(8):861-868 - PubMed

References

    1. PLoS One. 2011;6(7):e22859 - PubMed

References

    1. FASEB J. 2016 May;30(5):2058-63 - PubMed

References

    1. Annu Rev Biochem. 2004;73:355-82 - PubMed

References

    1. Nat Commun. 2010 May 04;1:13 - PubMed

References

    1. Mol Cell Biol. 2005 May;25(9):3483-91 - PubMed

References

    1. Cell. 2007 Sep 7;130(5):943-57 - PubMed

References

    1. Proc Natl Acad Sci U S A. 2009 Aug 4;106(31):13010-5 - PubMed

References

    1. Nature. 2009 Mar 12;458(7235):228-32 - PubMed

References

    1. Traffic. 2005 Feb;6(2):131-43 - PubMed

References

    1. Nat Cell Biol. 2009 Sep;11(9):1143-9 - PubMed

References

    1. PLoS One. 2008 Jan 23;3(1):e1487 - PubMed

References

    1. Genome Biol. 2011;12(4):220 - PubMed

References

    1. Proc Natl Acad Sci U S A. 2004 Jun 29;101(26):9683-8 - PubMed

References

    1. Science. 2012 Nov 16;338(6109):949-53 - PubMed

References

    1. EMBO J. 2004 May 5;23(9):1977-86 - PubMed

References

    1. J Proteome Res. 2014 Dec 5;13(12):5965-72 - PubMed

References

    1. Cell. 1997 Jan 10;88(1):97-107 - PubMed

References

    1. FASEB J. 1997 Nov;11(13):1067-75 - PubMed

References

    1. Cell. 2008 Jan 11;132(1):27-42 - PubMed

References

    1. Traffic. 2006 Aug;7(8):1017-31 - PubMed

References

    1. J Biol Chem. 2005 Jul 22;280(29):27004-12 - PubMed

References

    1. Cell. 2010 Aug 20;142(4):590-600 - PubMed

References

    1. Neuron. 1998 Oct;21(4):799-811 - PubMed

References

    1. PLoS One. 2018 Jul 18;13(7):e0200763 - PubMed

References

    1. J Biol Chem. 1983 Jul 10;258(13):8206-14 - PubMed

References

    1. J Immunol. 1996 Nov 15;157(10):4277-81 - PubMed

References

    1. Biol Cell. 2010 Mar 12;102(5):293-318 - PubMed

References

    1. Proc Natl Acad Sci U S A. 2017 Dec 12;114(50):13176-13181 - PubMed

References

    1. J Immunol. 1999 Aug 1;163(3):1274-81 - PubMed

References

    1. Neuropathology. 2010 Apr;30(2):103-12 - PubMed

References

    1. Biochem Biophys Res Commun. 2006 Dec 22;351(3):602-11 - PubMed

References

    1. Proc Natl Acad Sci U S A. 2006 Jan 31;103(5):1440-5 - PubMed

References

    1. Science. 2008 Feb 29;319(5867):1244-7 - PubMed

References

    1. J Cell Sci. 2007 Jan 1;120(Pt 1):191-9 - PubMed

References

    1. Nat Commun. 2014 May 13;5:3733 - PubMed

References

    1. Am J Physiol Lung Cell Mol Physiol. 2014 Jun 1;306(11):L1016-25 - PubMed

References

    1. PLoS One. 2008 Jul 30;3(7):e2809 - PubMed

References

    1. Nat Commun. 2018 Sep 26;9(1):3936 - PubMed

References

    1. Neuron. 1999 Jan;22(1):147-56 - PubMed

References

    1. Annu Rev Biochem. 2012;81:203-29 - PubMed

References

    1. Mol Biol Cell. 2000 Oct;11(10):3365-80 - PubMed

References

    1. Cancer Cell. 2011 Feb 15;19(2):168-76 - PubMed

References

    1. J Virol. 2001 Jun;75(12):5711-8 - PubMed

References

    1. Nat Cell Biol. 2012 Jun 03;14(7):677-85 - PubMed

References

    1. J Cell Biol. 2010 Sep 20;190(6):1079-91 - PubMed

References

    1. J Neurosci. 2015 Jul 29;35(30):10851-65 - PubMed

References

    1. Science. 2010 Sep 3;329(5996):1215-8 - PubMed

References

    1. Autophagy. 2016 Nov;12(11):2113-2128 - PubMed

References

    1. J Exp Med. 2002 May 20;195(10):1303-16 - PubMed

References

    1. J Biol Chem. 1987 Jul 5;262(19):9412-20 - PubMed

References

    1. Nat Commun. 2017 May 16;8:15287 - PubMed

References

    1. Int J Biochem Cell Biol. 2013 Oct;45(10):2333-47 - PubMed

References

    1. Genes Cells. 2004 Dec;9(12):1189-97 - PubMed

References

    1. Trends Mol Med. 2002 Jan;8(1):23-30 - PubMed

References

    1. Annu Rev Biochem. 2013;82:357-85 - PubMed

References

    1. Blood. 2007 Nov 1;110(9):3234-44 - PubMed

References

    1. Proc Natl Acad Sci U S A. 2011 Feb 1;108(5):1763-70 - PubMed

References

    1. Dev Cell. 2011 Oct 18;21(4):708-21 - PubMed

References

    1. FEBS Lett. 2009 Feb 4;583(3):591-4 - PubMed

References

    1. J Cell Biol. 2010 Apr 19;189(2):223-32 - PubMed

References

    1. PLoS One. 2011;6(12):e29460 - PubMed

References

    1. Nat Cell Biol. 2018 Mar;20(3):233-242 - PubMed

References

    1. J Biol Chem. 2003 Oct 3;278(40):39104-13 - PubMed

References

    1. Nat Commun. 2014 Mar 18;5:3477 - PubMed

References

    1. Genes Dev. 2007 Nov 15;21(22):2861-73 - PubMed

References

    1. Nature. 2017 Jun 22;546(7659):498-503 - PubMed

References

    1. Methods Mol Biol. 2017;1660:15-22 - PubMed

References

    1. Nat Commun. 2013;4:2980 - PubMed

References

    1. Cell. 1984 Aug;38(1):127-34 - PubMed

References

    1. Nature. 1998 Sep 24;395(6700):395-8 - PubMed

References

    1. J Pathol Transl Med. 2018 Jan;52(1):1-8 - PubMed

References

    1. Nature. 2009 Apr 9;458(7239):732-6 - PubMed

References

    1. Acta Neuropathol. 2015 May;129(5):695-713 - PubMed

References

    1. Nature. 2015 Nov 19;527(7578):329-35 - PubMed

References

    1. J Cell Biol. 2013 Feb 18;200(4):373-83 - PubMed

References

    1. Med Microbiol Immunol. 2013 Jun;202(3):215-27 - PubMed

References

    1. Nat Commun. 2016 Nov 24;7:13588 - PubMed

References

    1. Cell Mol Life Sci. 2018 Feb;75(4):757-773 - PubMed

References

    1. Nature. 2008 Feb 28;451(7182):1069-75 - PubMed

References

    1. Biochem Biophys Res Commun. 2000 Aug 2;274(2):565-70 - PubMed

References

    1. Semin Cell Dev Biol. 2015 Apr;40:8-16 - PubMed

References

    1. Mol Cell Biol. 2006 Jul;26(13):5180-9 - PubMed

References

    1. J Biol Chem. 2001 Sep 21;276(38):35334-43 - PubMed

References

    1. Genes Dev. 1995 Nov 15;9(22):2723-35 - PubMed

References

    1. Nature. 1979 Jun 7;279(5713):523-5 - PubMed

References

    1. FEBS J. 2009 Nov;276(21):6355-63 - PubMed

References

    1. J Immunol. 2001 Dec 15;167(12):6736-44 - PubMed

References

    1. Trends Cell Biol. 2016 Oct;26(10):733-744 - PubMed

References

    1. Nature. 2011 May 25;474(7350):173-8 - PubMed

References

    1. Nat Rev Mol Cell Biol. 2002 Dec;3(12):893-905 - PubMed

References

    1. J Biol Chem. 2013 Jun 14;288(24):17713-24 - PubMed

References

    1. Nat Rev Neurol. 2014 Feb;10(2):92-8 - PubMed

References

    1. Mol Cell Proteomics. 2013 Feb;12(2):343-55 - PubMed

References

    1. Med Oncol. 2012 Dec;29(4):2911-8 - PubMed

References

    1. Annu Rev Biophys. 2017 May 22;46:149-173 - PubMed

References

    1. Front Physiol. 2014 Jan 16;4:408 - PubMed

References

    1. J Biochem. 2006 Aug;140(2):147-54 - PubMed

References

    1. J Cell Sci. 2013 Dec 15;126(Pt 24):5553-65 - PubMed

References

    1. Cell Mol Life Sci. 2018 Jan;75(1):1-19 - PubMed

References

    1. Nat Struct Mol Biol. 2014 Oct;21(10):927-36 - PubMed

References

    1. Cell. 2003 Sep 19;114(6):689-99 - PubMed

References

    1. Brain Res Mol Brain Res. 2001 Dec 30;97(2):186-9 - PubMed

References

    1. Proteomics. 2010 Sep;10(17):3190-202 - PubMed

References

    1. Cell Metab. 2007 Dec;6(6):472-83 - PubMed

References

    1. Proteomics. 2011 Nov;11(22):4397-410 - PubMed

References

    1. Nat Neurosci. 2013 May;16(5):562-70 - PubMed

References

    1. J Neurosci. 2005 Jun 22;25(25):6016-24 - PubMed

References

    1. BMC Cancer. 2011 Mar 27;11:108 - PubMed

References

    1. Genetics. 2006 Sep;174(1):229-39 - PubMed

References

    1. Nat Cell Biol. 2007 Jun;9(6):654-9 - PubMed

References

    1. Science. 2000 Sep 15;289(5486):1925-8 - PubMed

References

    1. Virology. 2000 Mar 1;268(1):178-91 - PubMed

References

    1. Trends Neurosci. 1998 Dec;21(12):516-20 - PubMed

References

    1. J Cell Sci. 2012 Feb 1;125(Pt 3):531-7 - PubMed

References

    1. Proc Natl Acad Sci U S A. 2016 Feb 23;113(8):E968-77 - PubMed

References

    1. Cell Metab. 2007 Dec;6(6):458-71 - PubMed

References

    1. J Immunol. 2015 Sep 15;195(6):2722-30 - PubMed

References

    1. J Biol Chem. 2006 Sep 15;281(37):27145-57 - PubMed

References

    1. J Cell Biol. 2016 Jul 18;214(2):197-213 - PubMed

References

    1. Eur J Biochem. 1996 Feb 15;236(1):1-26 - PubMed

References

    1. Proteomes. 2019 May 23;7(2):null - PubMed

References

    1. J Virol. 2010 Aug;84(16):8181-92 - PubMed

References

    1. EMBO Rep. 2003 Dec;4(12):1169-74 - PubMed

References

    1. Cell. 2004 Apr 30;117(3):399-412 - PubMed

References

    1. Sci Rep. 2015 Jun 03;5:10300 - PubMed

References

    1. Biochem Soc Trans. 2010 Feb;38(Pt 1):34-9 - PubMed

References

    1. J Neurosci. 2010 May 19;30(20):6838-51 - PubMed

References

    1. FASEB J. 1997 Dec;11(14):1257-68 - PubMed

References

    1. J Neurosci. 2016 Feb 24;36(8):2425-37 - PubMed

References

    1. EMBO J. 2019 Mar 15;38(6):null - PubMed

References

    1. J Biol Chem. 2003 Oct 10;278(41):39517-26 - PubMed

References

    1. Cell Rep. 2013 Jul 11;4(1):124-34 - PubMed

References

    1. Nat Commun. 2015 Dec 03;6:10053 - PubMed

References

    1. Gen Physiol Biophys. 2015 Oct;34(4):337-52 - PubMed

References

    1. J Clin Invest. 2011 Feb;121(2):715-25 - PubMed

References

    1. J Am Soc Nephrol. 2009 Feb;20(2):363-79 - PubMed

References

    1. J Pathol. 2007 Apr;211(5):582-90 - PubMed

References

    1. Nat Rev Mol Cell Biol. 2009 Aug;10(8):564-8 - PubMed

References

    1. Science. 2001 Nov 23;294(5547):1704-8 - PubMed

References

    1. Int J Biochem Cell Biol. 2010 Jun;42(6):828-43 - PubMed

References

    1. Eukaryot Cell. 2003 Oct;2(5):930-6 - PubMed

References

    1. Science. 2004 Jan 23;303(5657):531-4 - PubMed

References

    1. Trends Cell Biol. 2018 Nov;28(11):926-940 - PubMed

References

    1. Nat Cell Biol. 2008 May;10(5):619-24 - PubMed

References

    1. Dev Cell. 2006 Mar;10(3):343-54 - PubMed

References

    1. N Engl J Med. 2013 Feb 14;368(7):651-62 - PubMed

References

    1. J Cell Biol. 1996 Dec;135(6 Pt 1):1457-70 - PubMed

References

    1. Sci Rep. 2018 Oct 15;8(1):15263 - PubMed

References

    1. Nat Rev Mol Cell Biol. 2001 Feb;2(2):107-17 - PubMed

References

    1. Genomics. 1996 Sep 1;36(2):271-9 - PubMed

References

    1. Nat Med. 2012 Jun;18(6):883-91 - PubMed

References

    1. J Cell Biol. 2004 Aug 16;166(4):487-92 - PubMed

References

    1. Mol Ther. 2017 Jun 7;25(6):1269-1278 - PubMed

References

    1. Nat Struct Mol Biol. 2014 Apr;21(4):301-7 - PubMed

References

    1. J Proteome Res. 2009 Jun;8(6):2851-62 - PubMed

References

    1. Mol Cell. 2009 May 15;34(3):259-69 - PubMed

References

    1. Mol Cell Proteomics. 2016 May;15(5):1556-71 - PubMed

References

    1. Nature. 2006 Nov 2;444(7115):115-8 - PubMed

References

    1. J Cell Sci. 2010 Nov 15;123(Pt 22):3849-55 - PubMed

References

    1. Nat Rev Mol Cell Biol. 2007 May;8(5):355-68 - PubMed

References

    1. Mol Cell. 1998 Aug;2(2):233-9 - PubMed

References

    1. Traffic. 2010 May;11(5):675-87 - PubMed

References

    1. Int J Biochem Cell Biol. 2010 Oct;42(10):1618-21 - PubMed

References

    1. Cell Adh Migr. 2011 Mar-Apr;5(2):187-98 - PubMed

References

    1. J Biol Chem. 2014 Aug 8;289(32):22258-67 - PubMed

References

    1. Curr Opin Cell Biol. 2008 Aug;20(4):437-44 - PubMed

References

    1. Curr Alzheimer Res. 2018 Feb 22;15(4):313-335 - PubMed

References

    1. Genes Cells. 2010 Sep 1;15(9):923-33 - PubMed

References

    1. Mol Hum Reprod. 2005 Jan;11(1):35-41 - PubMed

References

    1. Sci Signal. 2012 Dec 04;5(253):ra88 - PubMed

References

    1. Annu Rev Cell Dev Biol. 2014;30:255-89 - PubMed

References

    1. J Biol Chem. 2006 Aug 11;281(32):23083-91 - PubMed

References

    1. J Cell Sci. 2012 Mar 1;125(Pt 5):1129-40 - PubMed

References

    1. Nature. 2018 Nov;563(7732):508-513 - PubMed

References

    1. Nat Rev Mol Cell Biol. 2005 Jan;6(1):9-20 - PubMed

References

    1. Nat Cell Biol. 2015 Mar;17(3):300-10 - PubMed

References

    1. J Biol Chem. 2001 May 11;276(19):15893-7 - PubMed

References

    1. Brain. 2018 Jul 1;141(7):1934-1945 - PubMed

References

    1. Oncogene. 1996 Sep 5;13(5):971-82 - PubMed

References

    1. Mol Biol Cell. 1999 May;10(5):1367-79 - PubMed

References

    1. Biochem J. 2004 Aug 15;382(Pt 1):13-25 - PubMed

References

    1. J Biol Chem. 2010 Feb 19;285(8):5417-27 - PubMed

References

    1. J Biol Chem. 2011 Apr 29;286(17):14913-21 - PubMed

References

    1. Virology. 2007 Apr 10;360(2):461-8 - PubMed

References

    1. Blood Cells Mol Dis. 2005 Nov-Dec;35(3):398-403 - PubMed

References

    1. Nat Commun. 2011 Feb 08;2:181 - PubMed

References

    1. J Cell Biol. 2011 Jul 11;194(1):49-60 - PubMed

References

    1. J Biol Chem. 2008 Nov 21;283(47):32621-7 - PubMed

References

    1. Dev Cell. 2009 Jul;17(1):87-97 - PubMed

References

    1. Arch Biochem Biophys. 2011 May 15;509(2):164-9 - PubMed

References

    1. Proc Natl Acad Sci U S A. 2006 Jul 25;103(30):11172-7 - PubMed

References

    1. Nat Chem. 2017 Aug;9(8):751-761 - PubMed

References

    1. Proc Natl Acad Sci U S A. 2004 Sep 7;101(36):13368-73 - PubMed

References

    1. EMBO J. 1996 May 15;15(10):2371-80 - PubMed

References

    1. Traffic. 2009 Jul;10(7):925-37 - PubMed

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