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PMID: 20837771 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

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

The Journal of cell biology ·Vol. 190 ·No. 6 ·2010-09-20 ·Pages 1079-91

Chairoungdua A, Smith DL, Pochard P, Hull M, Caplan MJ

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.

MeSH Terms
Animals Antigens, CD/metabolism Cadherins/metabolism Cell Line Exosomes/metabolism,ultrastructure Gene Knockdown Techniques Genes, Reporter/genetics Glycogen Synthase Kinase 3/metabolism Glycogen Synthase Kinase 3 beta Humans Kangai-1 Protein/metabolism Lysosomes/metabolism Membrane Glycoproteins/metabolism Mice Models, Biological Proteasome Endopeptidase Complex/metabolism Protein Processing, Post-Translational Protein Stability Protein Transport Signal Transduction Tetraspanin 29 Transfection Wnt Proteins/metabolism beta Catenin/metabolism
Chemicals
Antigens, CD CD82 protein, human CD9 protein, human Cadherins Cd9 protein, mouse Kangai-1 Protein Membrane Glycoproteins Tetraspanin 29 Wnt Proteins beta Catenin GSK3B protein, human Glycogen Synthase Kinase 3 beta Gsk3b protein, mouse Glycogen Synthase Kinase 3 Proteasome Endopeptidase Complex
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Chairoungdua Arthit
Department of Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, CT 06510, USA.
Smith Danielle L
Pochard Pierre
Hull Michael
Caplan Michael J
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
1540-8140
DOI
10.1083/jcb.201002049
Published
2010-09-20
Epub
2010-00-13
Pages
1079-91
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC3101591
Subset
IM
Grants
NIDDK NIH HHS · P50 DK057328 · United States
NIDDK NIH HHS · DK-17433 · United States
NIDDK NIH HHS · DK-57328 · United States
NIDDK NIH HHS · P01 DK017433 · United States
NIDDK NIH HHS · R01 DK072614 · United States
Corrections
CommentIn
PMID: 21080585
External Links
PubMed source DOI: 10.1083/jcb.201002049 PMC Full Text View journal details
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