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Mulcahy LA, Pink RC, Carter DR, et al. Routes and mechanisms of extracellular vesicle uptake. J Extracell Vesicles. 2014;3doi: 10.3402/jev.v3.24641.
Mulcahy, L. A., Pink, R. C., Carter, D. R., & Scholte, J. A. (2014). Routes and mechanisms of extracellular vesicle uptake. Journal of extracellular vesicles, 3. https://doi.org/10.3402/jev.v3.24641
Mulcahy, Laura Ann, et al. "Routes and mechanisms of extracellular vesicle uptake." Journal of extracellular vesicles vol. 3 (2014). doi: https://doi.org/10.3402/jev.v3.24641
Mulcahy LA, Pink RC, Carter DR, Scholte JA. Routes and mechanisms of extracellular vesicle uptake. J Extracell Vesicles. 2014 Aug 04;3. doi: 10.3402/jev.v3.24641. eCollection 2014. PMID: 25143819; PMCID: PMC4122821.
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J Extracell Vesicles. 2014 Aug 04;3. doi: 10.3402/jev.v3.24641. eCollection 2014.

Routes and mechanisms of extracellular vesicle uptake.

Journal of extracellular vesicles

Laura Ann Mulcahy, Ryan Charles Pink, David Raul Francisco Carter, Scholte

Affiliations

  1. Department of Biological and Medical Science, Faculty of Health and Life Sciences, Oxford Brookes University, Oxford, UK.

PMID: 25143819 PMCID: PMC4122821 DOI: 10.3402/jev.v3.24641

Abstract

Extracellular vesicles (EVs) are small vesicles released by donor cells that can be taken up by recipient cells. Despite their discovery decades ago, it has only recently become apparent that EVs play an important role in cell-to-cell communication. EVs can carry a range of nucleic acids and proteins which can have a significant impact on the phenotype of the recipient. For this phenotypic effect to occur, EVs need to fuse with target cell membranes, either directly with the plasma membrane or with the endosomal membrane after endocytic uptake. EVs are of therapeutic interest because they are deregulated in diseases such as cancer and they could be harnessed to deliver drugs to target cells. It is therefore important to understand the molecular mechanisms by which EVs are taken up into cells. This comprehensive review summarizes current knowledge of EV uptake mechanisms. Cells appear to take up EVs by a variety of endocytic pathways, including clathrin-dependent endocytosis, and clathrin-independent pathways such as caveolin-mediated uptake, macropinocytosis, phagocytosis, and lipid raft-mediated internalization. Indeed, it seems likely that a heterogeneous population of EVs may gain entry into a cell via more than one route. The uptake mechanism used by a given EV may depend on proteins and glycoproteins found on the surface of both the vesicle and the target cell. Further research is needed to understand the precise rules that underpin EV entry into cells.

Keywords: EV internalization; EV uptake; cell communication; cell–EV interaction; endocytosis; exosomes; extracellular vesicles

References

  1. Curr Biol. 1999 Mar 11;9(5):257-60 - PubMed
  2. Oncogene. 2006 May 18;25(21):2961-73 - PubMed
  3. Blood. 2012 Jan 19;119(3):756-66 - PubMed
  4. Int J Biochem Cell Biol. 2012 Sep;44(9):1574-84 - PubMed
  5. Nature. 2002 May 9;417(6885):182-7 - PubMed
  6. Nat Rev Mol Cell Biol. 2007 Mar;8(3):185-94 - PubMed
  7. J Virol. 2013 Sep;87(18):10334-47 - PubMed
  8. Cell. 2003 Feb 21;112(4):519-33 - PubMed
  9. PLoS Biol. 2012;10(4):e1001302 - PubMed
  10. Radiat Res. 2012 May;177(5):539-45 - PubMed
  11. Radiol Oncol. 2013 Jul 30;47(3):197-205 - PubMed
  12. Nature. 2001 Mar 8;410(6825):231-5 - PubMed
  13. Genes Dev. 2007 Mar 15;21(6):644-8 - PubMed
  14. Nat Cell Biol. 2006 Jan;8(1):46-54 - PubMed
  15. Biomed Res Int. 2014;2014:619829 - PubMed
  16. Nat Cell Biol. 2002 Sep;4(9):691-8 - PubMed
  17. J Cell Biochem. 2010 Oct 1;111(2):488-96 - PubMed
  18. Biochem J. 2006 Feb 1;393(Pt 3):609-18 - PubMed
  19. Annu Rev Biochem. 1998;67:199-225 - PubMed
  20. Curr Top Microbiol Immunol. 2010;347:263-78 - PubMed
  21. Annu Rev Biochem. 1999;68:863-911 - PubMed
  22. J Cell Biol. 1993 Dec;123(5):1107-17 - PubMed
  23. Ciba Found Symp. 1993;176:185-93; discussion 193-7 - PubMed
  24. Nature. 1981 Sep 24;293(5830):302-5 - PubMed
  25. J Biol Chem. 2011 Sep 2;286(35):30911-30925 - PubMed
  26. Neoplasia. 2009 Oct;11(10):1093-105 - PubMed
  27. Cell. 1999 Oct 1;99(1):13-22 - PubMed
  28. PLoS One. 2013 Nov 14;8(11):e80844 - PubMed
  29. Pharmaceuticals (Basel). 2013;6(5):659-80 - PubMed
  30. Exp Cell Res. 2000 Nov 1;260(2):292-303 - PubMed
  31. J Cell Sci. 2011 Feb 1;124(Pt 3):447-58 - PubMed
  32. Annu Rev Biochem. 2009;78:857-902 - PubMed
  33. Curr Biol. 2007 Jul 3;17(13):1151-6 - PubMed
  34. Front Biosci. 2008 Jan 01;13:462-76 - PubMed
  35. J Cell Biol. 1994 Nov;127(4):915-34 - PubMed
  36. J Immunother. 2011 Nov-Dec;34(9):611-28 - PubMed
  37. Nat Rev Cancer. 2009 Jan;9(1):40-55 - PubMed
  38. Proc Natl Acad Sci U S A. 2002 Jan 8;99(1):167-72 - PubMed
  39. Blood Cells Mol Dis. 2006 Mar-Apr;36(2):315-21 - PubMed
  40. J Biol Chem. 1997 May 23;272(21):13793-802 - PubMed
  41. Blood. 2004 Nov 15;104(10):3257-66 - PubMed
  42. J Immunol. 2003 Mar 15;170(6):3037-45 - PubMed
  43. J Cell Biol. 1993 Aug;122(3):565-78 - PubMed
  44. Mol Cell Biol. 1999 Feb;19(2):1410-5 - PubMed
  45. J Biol Chem. 1997 Aug 15;272(33):20332-5 - PubMed
  46. Nat Rev Mol Cell Biol. 2005 Oct;6(10):801-11 - PubMed
  47. Blood. 2009 Feb 26;113(9):1977-81 - PubMed
  48. Trends Cell Biol. 2008 May;18(5):199-209 - PubMed
  49. PLoS One. 2009;4(4):e5219 - PubMed
  50. Dev Biol. 2006 Feb 15;290(2):351-8 - PubMed
  51. Traffic. 2009 Apr;10(4):364-71 - PubMed
  52. J Lipid Mediat Cell Signal. 1996 Sep;14(1-3):259-61 - PubMed
  53. Nat Med. 1998 May;4(5):594-600 - PubMed
  54. J Biol Chem. 1980 Feb 10;255(3):835-8 - PubMed
  55. Nat Biotechnol. 2011 Apr;29(4):341-5 - PubMed
  56. J Cell Biol. 2003 May 26;161(4):673-7 - PubMed
  57. J Cell Physiol. 1981 Aug;108(2):195-211 - PubMed
  58. J Biol Chem. 2009 Dec 4;284(49):34211-22 - PubMed
  59. J Cell Sci. 1996 May;109 ( Pt 5):941-52 - PubMed
  60. Exp Hematol. 2010 Mar;38(3):233-45 - PubMed
  61. Science. 2002 May 31;296(5573):1655-7 - PubMed
  62. Blood. 2010 Jan 21;115(3):696-705 - PubMed
  63. Am J Reprod Immunol. 2011 Oct;66(4):259-69 - PubMed
  64. J Biol Chem. 1994 Mar 18;269(11):8362-5 - PubMed
  65. Kidney Int. 2010 Nov;78(9):838-48 - PubMed
  66. Int J Cancer. 2005 Feb 20;113(5):752-60 - PubMed
  67. J Virol. 2000 Oct;74(19):9240-4 - PubMed
  68. Biochem Soc Trans. 2011 Apr;39(2):559-62 - PubMed
  69. Biol Reprod. 2009 Oct;81(4):717-29 - PubMed
  70. Cell Commun Signal. 2012 Nov 28;10(1):37 - PubMed
  71. Nat Commun. 2012;3:1282 - PubMed
  72. Dig Liver Dis. 2009 Dec;41(12):875-80 - PubMed
  73. J Cell Physiol. 2013 Jul;228(7):1487-95 - PubMed
  74. J Clin Invest. 2002 Sep;110(5):597-603 - PubMed
  75. Nat Struct Mol Biol. 2008 Jul;15(7):675-83 - PubMed
  76. Biochim Biophys Acta. 1987 Oct 5;906(3):309-52 - PubMed
  77. J Cell Biol. 2013 Feb 18;200(4):373-83 - PubMed
  78. Semin Cell Dev Biol. 2006 Apr;17(2):254-63 - PubMed
  79. Cancer Lett. 2009 Jun 8;278(1):73-81 - PubMed
  80. PLoS One. 2012;7(5):e36395 - PubMed
  81. Proc Natl Acad Sci U S A. 2012 Jul 31;109(31):E2110-6 - PubMed
  82. Eur Biophys J. 2007 Nov;36(8):887-99 - PubMed
  83. Immunology. 2007 Jan;120(1):90-102 - PubMed
  84. J Biol Chem. 2013 Jun 14;288(24):17713-24 - PubMed
  85. Biochim Biophys Acta. 2008 Sep;1779(9):558-65 - PubMed
  86. J Cell Sci. 2002 Jul 15;115(Pt 14):2953-62 - PubMed
  87. Am J Pathol. 2009 Aug;175(2):696-705 - PubMed
  88. Curr Opin Cell Biol. 2002 Apr;14(2):203-13 - PubMed
  89. Oncotarget. 2013 Nov;4(11):2057-66 - PubMed
  90. Cell. 1987 Dec 4;51(5):813-9 - PubMed
  91. J Immunol. 1992 Apr 1;148(7):2207-16 - PubMed
  92. Curr Opin Cell Biol. 1999 Aug;11(4):424-31 - PubMed
  93. Traffic. 2008 Jun;9(6):871-81 - PubMed
  94. Proc Natl Acad Sci U S A. 2013 Oct 22;110(43):17380-5 - PubMed
  95. J Cell Biol. 1997 Apr 7;137(1):1-4 - PubMed
  96. Nat Rev Mol Cell Biol. 2008 Aug;9(8):639-49 - PubMed
  97. J Cell Sci. 2010 Mar 15;123(Pt 6):842-52 - PubMed
  98. Biochim Biophys Acta. 2014 Jan;1841(1):108-20 - PubMed
  99. J Cell Biol. 2003 Jun 9;161(5):945-56 - PubMed
  100. BMC Cancer. 2011 Mar 27;11:108 - PubMed
  101. Nat Cell Biol. 2007 Jun;9(6):654-9 - PubMed
  102. Proc Natl Acad Sci U S A. 2010 Apr 6;107(14):6328-33 - PubMed
  103. Gut. 2012 Sep;61(9):1330-9 - PubMed
  104. PLoS One. 2011;6(9):e24234 - PubMed
  105. AIDS. 2014 Jan 14;28(2):171-80 - PubMed
  106. Cell. 2004 Sep 3;118(5):591-605 - PubMed
  107. Blood. 1999 Dec 1;94(11):3791-9 - PubMed
  108. Biochim Biophys Acta. 2012 Aug;1826(1):103-11 - PubMed
  109. Vaccine. 2008 Jul 4;26(29-30):3662-72 - PubMed
  110. J Biol Chem. 2001 Oct 12;276(41):38121-38 - PubMed
  111. Curr Top Microbiol Immunol. 2009;339:85-102 - PubMed
  112. Proc Natl Acad Sci U S A. 2003 May 27;100(11):6670-5 - PubMed
  113. Am J Pathol. 2006 Dec;169(6):2127-36 - PubMed
  114. J Biol Chem. 1991 Aug 5;266(22):14486-90 - PubMed
  115. Nat Rev Immunol. 2005 Feb;5(2):136-48 - PubMed
  116. Immunobiology. 2007;212(9-10):785-93 - PubMed
  117. Proc Natl Acad Sci U S A. 2006 Nov 21;103(47):17955-60 - PubMed
  118. Blood. 2009 Mar 19;113(12):2732-41 - PubMed
  119. Nature. 2007 Nov 15;450(7168):435-9 - PubMed
  120. Exp Cell Res. 2003 Nov 15;291(1):150-66 - PubMed
  121. J Biol Chem. 1998 Aug 7;273(32):20121-7 - PubMed
  122. J Biol Chem. 2012 Mar 30;287(14):10977-89 - PubMed
  123. J Cell Biol. 1996 Dec;135(5):1249-60 - PubMed
  124. J Cell Biol. 1983 Jan;96(1):1-27 - PubMed
  125. Trends Cell Biol. 1995 Mar;5(3):93-9 - PubMed
  126. J Cell Sci. 2011 Dec 1;124(Pt 23):3933-40 - PubMed
  127. J Virol. 2009 May;83(9):4354-64 - PubMed
  128. J Cell Sci. 1999 May;112 ( Pt 9):1303-11 - PubMed
  129. PLoS One. 2008 Jun 11;3(6):e2416 - PubMed
  130. Eur J Immunol. 2004 Sep;34(9):2620-9 - PubMed
  131. J Biol Chem. 1999 Apr 30;274(18):12702-9 - PubMed
  132. Annu Rev Biochem. 2000;69:699-727 - PubMed
  133. Curr Biol. 2008 Nov 25;18(22):1802-8 - PubMed
  134. Trends Immunol. 2013 Oct;34(10):482-6 - PubMed
  135. Eur J Immunol. 2003 Feb;33(2):522-31 - PubMed
  136. Traffic. 2010 May;11(5):675-87 - PubMed
  137. J Exp Med. 1996 Mar 1;183(3):1161-72 - PubMed
  138. Mol Biol Cell. 2009 Nov;20(22):4630-9 - PubMed
  139. Vaccine. 2011 Apr 27;29(19):3538-47 - PubMed
  140. Blood Rev. 2013 Jan;27(1):31-9 - PubMed
  141. Trends Cell Biol. 2006 Oct;16(10):522-9 - PubMed
  142. Cancer Res. 2010 Feb 15;70(4):1668-78 - PubMed
  143. J Proteomics. 2010 Sep 10;73(10):1907-20 - PubMed
  144. J Cell Biol. 1999 Nov 1;147(3):599-610 - PubMed
  145. Curr Biol. 1999 Mar 11;9(5):261-4 - PubMed
  146. J Transl Med. 2011 Jun 08;9:86 - PubMed
  147. Cell. 2008 Oct 31;135(3):510-23 - PubMed
  148. Nature. 2010 May 27;465(7297):435-40 - PubMed
  149. Development. 2002 Apr;129(8):1995-2002 - PubMed
  150. J Immunol. 2010 Nov 1;185(9):5268-78 - PubMed
  151. J Cell Biol. 1985 Apr;100(4):1173-84 - PubMed
  152. Blood. 2009 Feb 26;113(9):1957-66 - PubMed
  153. Proc Natl Acad Sci U S A. 2004 Feb 3;101(5):1297-302 - PubMed
  154. Pharmacol Rev. 1998 Jun;50(2):197-263 - PubMed

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