WLS:WNT complex is internalized for maturation into exosomes

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R-HSA-3781943
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Reaction [omitted]
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Homo sapiens
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Fractionation of extracellular WNT activity shows that between 12-40% of secreted WNT ligand is present on exosomal vesicles (Gross et al, 2012; Beckett et al, 2013). Exosomes are 40 - 100 nm microvesicles of endocytic origin with established roles in cell-cell communication. They are produced by multivesicular bodies (MVBs) and directed to the plasma membrane for secretion (reviewed in Simons and Raposo, 2009). WNT secretion in the exosomal fraction is dependent on WLS/EVI/SPR in both human and Drosophila cells (Gross et al, 2012; Beckett et al, 2013). While exosomes have been shown to be required for presynaptic release of EVI and Wg at Drosophila neuromuscular junctions, there is conflicting evidence about whether they play a role in the formation of a Wg gradient at the Drosophila imaginal disc (Korkut et al, 2009; Gross et al, 2012; Beckett et al, 2013). Exosomal WNT fractions co-purify with TSG101 and other components of the ESCRT machinery, and knockdown of ESCRT 0 components reduces the levels of WNT3A and the signaling activity of the exosomal fractions (Gross et al, 2012; Beckett et al, 2013).

Literature References
PubMed ID Title Journal Year
22983114 Active Wnt proteins are secreted on exosomes

Gross, JC, Chaudhary, V, Bartscherer, K, Boutros, M

Nat. Cell Biol. 2012
19442504 Exosomes--vesicular carriers for intercellular communication

Simons, M, Raposo, G

Curr. Opin. Cell Biol. 2009
19837038 Trans-synaptic transmission of vesicular Wnt signals through Evi/Wntless

Korkut, C, Ataman, B, Ramachandran, P, Ashley, J, Barria, R, Gherbesi, N, Budnik, V

Cell 2009
23260141 Exosomes mediate stromal mobilization of autocrine Wnt-PCP signaling in breast cancer cell migration

Luga, V, Zhang, L, Viloria-Petit, AM, Ogunjimi, AA, Inanlou, MR, Chiu, E, Buchanan, M, Hosein, AN, Basik, M, Wrana, JL

Cell 2012
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