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Exosome release of β-catenin: a novel mechanism that antagonizes Wnt signaling.

Abstract : CD82 and CD9 are tetraspanin membrane proteins that can function as suppressors of tumor metastasis. Expression of CD9 and CD82 in transfected cells strongly suppresses β-catenin-mediated Wnt signaling activity and induces a significant decrease in β-catenin protein levels. Inhibition of Wnt/β-catenin signaling is independent of glycogen synthase kinase-3β and of the proteasome- and lysosome-mediated protein degradation pathways. CD82 and CD9 expression induces β-catenin export via exosomes, which is blocked by a sphingomyelinase inhibitor, GW4869. CD82 fails to induce exosome release of β-catenin in cells that express low levels of E-cadherin. Exosome release from dendritic cells generated from CD9 knockout mice is reduced compared with that from wild-type dendritic cells. These results suggest that CD82 and CD9 down-regulate the Wnt signaling pathway through the exosomal discharge of β-catenin. Thus, exosomal packaging and release of cytosolic proteins can modulate the activity of cellular signaling pathways.
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Arthit Chairoungdua, Danielle L Smith, Pierre Pochard, Michael Hull, Michael J Caplan. Exosome release of β-catenin: a novel mechanism that antagonizes Wnt signaling.. Journal of Cell Biology, Rockefeller University Press, 2010, 190 (6), pp.1079-91. ⟨hal-01134267⟩

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