TABLE 1.
Molecules involved in the biogenesis and secretion of exosomes.
| Molecules | Cell lines | Functions | References |
| ESCRT-dependent pathway | |||
| ESCRT-0 | |||
| HRS | HeLa cells, HEK293 cells, Head and neck squamous cell carcinoma, Mouse dendritic cells | Depletion of HRS can reduce the exosome secretion | Tamai et al., 2010; Gross et al., 2012; Colombo et al., 2013; Hoshino et al., 2013 |
| STAM | HeLa cells | Depletion of STAM1 can reduce exosome secretion | Colombo et al., 2013 |
| ESCRT-I | |||
| TSG101 | HeLa cells, MCF-7 cells | Knockdown of TSG101 results in reduced exosome secretion | Baietti et al., 2012; Colombo et al., 2013 |
| ESCRT-II | HeLa cells | unclear | |
| ESCRT-III | |||
| CHMP4 | MCF-7 cells | Knockdown of the ESCRT-III component CHMP4 can decrease exosome secretion | Baietti et al., 2012 |
| Accessory proteins | |||
| ALIX | HeLa cells | Silencing of ALIX does not affect the number of exosomes secreted, but changes the protein composition of exosomes, increasing the number of MCH class II molecules in cells and exosomes | Colombo et al., 2013 |
| Mouse dendritic cells | Silencing of ALIX reduced exosomes containing MHC class II, CD63, and CD81 in approximately half of the cells | Tamai et al., 2010 | |
| MCF-7 cells | The syndecan–syntenin–ALIX interaction was necessary for biogenesis of exosomes | Friand et al., 2015 | |
| VPS4 | HeLa cells | Inhibition of VPS4B led to increased exosome secretion | Colombo et al., 2013 |
| MCF-7 cells | Simultaneously inhibition of VSP4A and VSP4B reduced exosome secretion | Baietti et al., 2012 | |
| ESCRT-independent pathway | |||
| Lipids | |||
| Ceramide | Oligodendroglia cells | Inhibition of sphingomyelinase can impair the synthesis of ceramide, thus disrupting the secretion of exosomes | Trajkovic et al., 2008 |
| Phospholipase D2(PLD2) | RBL-2H3 cells | Inhibition of PLD2 can impair the synthesis of PA, thus disrupting the secretion of exosomes | Laulagnier et al., 2004 |
| Cholesterol | Oligodendroglia cells | Accumulation of cholesterol in MVBs can induce secretion of exosomes expressing CD63, ALIX, and Flotillin-2, from oligodendroglia cells | Strauss et al., 2010 |
| Tetraspanin family | |||
| CD9 | HEK293 cells | CD9 has been shown to increase exosome secretion | Chairoungdua et al., 2010 |
| Dendritic cells | In the CD9 knockout mouse, secretion of exosomes expressing flotillin-1 is decreased from bone marrow dendritic cells. | Chairoungdua et al., 2010 | |
| CD63 | Melanoma cells | CD63 has been shown to sort the melanosomal protein PMEL into ILVs | Van Niel et al., 2011 |
| CD81 | Lymphoblasts | CD81 ligands are transported to exosomes for secretion | Perez-Hernandez et al., 2013 |
| CD82 | HEK293 cells | CD82 has been shown to increase exosome secretion | Chairoungdua et al., 2010 |
| TSPAN8 | Rat adenocarcinoma cells | Overexpression of TSPAN8 changed the mRNA and protein constituents in exosomes, without affecting the amount of exosome secretion | Nazarenko et al., 2010 |
| Chaperone | |||
| Hsc70 | Reticulocytes | Hsc70 was shown to recruit transferrin receptor (TFR) in mature reticulocytes | Géminard et al., 2004 |
| Rab GTPase family | |||
| Rab2B, Rab5A, Rab9A | HeLa cells | knockdown of Rab2B, Rab5A, and Rab9A can reduce the secretion of exosomes | Ostrowski et al., 2010 |
| Rab7 | HeLa cells | Knockdown of Rab7 dis not influence exosome secretion | Ostrowski et al., 2010 |
| MCF-7 cells | Rab7 is involved in the release of exosomes containing syntenin and ALIX | Baietti et al., 2012 | |
| Rab11 | HeLa cells | Knockdown of Rab11A did not influence exosome secretion | Ostrowski et al., 2010 |
| K562 cells | Rab11 was linked to the exosome secretion involving TFR and Hsc70 | Savina et al., 2002 | |
| RPE1 cells | Rab11 is involved in the release of exosomes containing anthrax toxin | Abrami et al., 2013 | |
| Rab27A or Rab27B | HeLa cells | Depletion of Rab27A or Rab27B, located in late endosomes and lysosome-related organelles, strikingly decreased the amount of exosome secretion | Ostrowski et al., 2010 |
| Rab35 | Oligodendroglia cells, Oli-neu cells | Knockdown of Rab35 interferes with the processing of PLP-expressing exosomes in oli-neu cells and primary oligodendrocytes | Hsu et al., 2010; Frühbeis et al., 2013 |
| RPE1 cells | Rab35 is involved in the release of exosomes containing anthrax toxin | Abrami et al., 2013 | |
| SNAREs family | |||
| VAMP7 | K562 erythroleukemia cells | Exosome secretion depends on v-SNARE protein VAMP7 | Fader et al., 2009 |
| MDCK cells | Inhibition of VAMP7 disrupted release of lysosomes but not secretion of exosomes | Proux-Gillardeaux et al., 2007 | |
| YKT6 | HEK293 cells | v-SNARE protein YKT6 is essential for release of exosomes containing the WNT3A morphogen | Gross et al., 2012 |