Arthit ChairoungduaDanielle L. SmithPierre PochardMichael HullMichael J. CaplanYale University School of MedicineMahidol University2018-09-242018-09-242010-09-20Journal of Cell Biology. Vol.190, No.6 (2010), 1079-109100219525002195252-s2.0-77957195392https://repository.li.mahidol.ac.th/handle/123456789/28637CD82 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. © 2010 Chairoungdua et al.Mahidol UniversityBiochemistry, Genetics and Molecular BiologyArticleSCOPUS10.1083/jcb.201002049