Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Logo for

J. Cell Biol. 190 (6): 1079-1091

Copyright © 2010 by the Rockefeller University Press.


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

Arthit Chairoungdua1,2, Danielle L. Smith1, Pierre Pochard1, Michael Hull1, , and Michael J. Caplan1

1 Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, CT 06510
2 Department of Physiology, Faculty of Science, Mahidol University, Bangkok 10400, Thailand

Correspondence to Michael J. Caplan: michael.caplan{at}

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.

Abbreviations: BMDC, bone marrow dendritic cell • ESCRT, endosomal sorting complex required for transport • GSK-3β, glycogen synthase kinase-3β • MVB, multivesicular body

Targeting Wnt signaling at the neuroimmune interface for dopaminergic neuroprotection/repair in Parkinson's disease.
F. L'Episcopo, C. Tirolo, S. Caniglia, N. Testa, M. C. Morale, M. F. Serapide, S. Pluchino, and B. Marchetti (2014)
J Mol Cell Biol 6, 13-26
   Abstract »    Full Text »    PDF »
Extracellular vesicles: communication, coercion, and conditioning.
D. A. Shifrin Jr., M. D. Beckler, R. J. Coffey, and M. J. Tyska (2013)
Mol. Biol. Cell 24, 1253-1259
   Abstract »    Full Text »    PDF »
The Intracellular Interactome of Tetraspanin-enriched Microdomains Reveals Their Function as Sorting Machineries toward Exosomes.
D. Perez-Hernandez, C. Gutierrez-Vazquez, I. Jorge, S. Lopez-Martin, A. Ursa, F. Sanchez-Madrid, J. Vazquez, and M. Yanez-Mo (2013)
J. Biol. Chem. 288, 11649-11661
   Abstract »    Full Text »    PDF »
Tetraspanin18 is a FoxD3-responsive antagonist of cranial neural crest epithelial-to-mesenchymal transition that maintains cadherin-6B protein.
C. L. Fairchild and L. S. Gammill (2013)
J. Cell Sci. 126, 1464-1476
   Abstract »    Full Text »    PDF »
Reciprocal Negative Regulation between the Guanine Nucleotide Exchange Factor C3G and {beta}-Catenin.
K. Dayma, A. Ramadhas, K. Sasikumar, and V. Radha (2013)
Genes & Cancer
   Abstract »    Full Text »    PDF »
Coordinate regulation of N-glycosylation gene DPAGT1, canonical Wnt signaling and E-cadherin adhesion.
P. K. Sengupta, M. P. Bouchie, M. Nita-Lazar, H.-Y. Yang, and M. A. Kukuruzinska (2013)
J. Cell Sci. 126, 484-496
   Abstract »    Full Text »    PDF »
A Phytoestrogen Diarylheptanoid Mediates Estrogen Receptor/Akt/Glycogen Synthase Kinase 3{beta} Protein-dependent Activation of the Wnt/{beta}-Catenin Signaling Pathway.
K. Bhukhai, K. Suksen, N. Bhummaphan, K. Janjorn, N. Thongon, D. Tantikanlayaporn, P. Piyachaturawat, A. Suksamrarn, and A. Chairoungdua (2012)
J. Biol. Chem. 287, 36168-36178
   Abstract »    Full Text »    PDF »
Exosome release of ADAM15 and the functional implications of human macrophage-derived ADAM15 exosomes.
H. D. Lee, B.-H. Koo, Y. H. Kim, O.-H. Jeon, and D.-S. Kim (2012)
FASEB J 26, 3084-3095
   Abstract »    Full Text »    PDF »
Classification, Functions, and Clinical Relevance of Extracellular Vesicles.
E. van der Pol, A. N. Boing, P. Harrison, A. Sturk, and R. Nieuwland (2012)
Pharmacol. Rev. 64, 676-705
   Abstract »    Full Text »    PDF »
Microvesicles and Viral Infection.
D. G. Meckes Jr. and N. Raab-Traub (2011)
J. Virol. 85, 12844-12854
   Abstract »    Full Text »    PDF »
Scientific Frontiers: Emerging Technologies for Salivary Diagnostics.
B. J. Baum, J. R. Yates III, S. Srivastava, D. T. W. Wong, and J. E. Melvin (2011)
Advances in Dental Research 23, 360-368
   Abstract »    Full Text »    PDF »
LMP1 association with CD63 in endosomes and secretion via exosomes limits constitutive NF-{kappa}B activation.
F. J. Verweij, M. A. J. van Eijndhoven, E. S. Hopmans, T. Vendrig, T. Wurdinger, E. Cahir-McFarland, E. Kieff, D. Geerts, R. van der Kant, J. Neefjes, et al. (2011)
EMBO J. 30, 2115-2129
   Abstract »    Full Text »    PDF »
The Tetraspanin CD82 Is Specifically Recruited to Fungal and Bacterial Phagosomes prior to Acidification.
K. Artavanis-Tsakonas, P. V. Kasperkovitz, E. Papa, M. L. Cardenas, N. S. Khan, A. G. Van der Veen, H. L. Ploegh, and J. M. Vyas (2011)
Infect. Immun. 79, 1098-1106
   Abstract »    Full Text »    PDF »
{beta}-Catenin gets an honorable discharge.
B. Short (2010)
J. Cell Biol. 190, 945
   Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882