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.

Sci. Signal., 28 September 2010
Vol. 3, Issue 141, p. ec294
[DOI: 10.1126/scisignal.3141ec294]

EDITORS' CHOICE

Cell Biology Exit by Exosome

Wei Wong

Science Signaling, AAAS, Washington, DC 20005, USA

Tetraspanins are transmembrane proteins that show decreased abundance in various tumors. In contrast, increased abundance of β-catenin is associated with colon cancer. Basal phosphorylation by glycogen synthase 3β (GSK-3β) targets β-catenin for proteosomal degradation; signals that prevent GSK-3β phosphorylation enable the nuclear translocation of stabilized β-catenin and initiation of gene transcription. Previous microarray analysis suggested that the tetraspanin CD9 may inhibit Wnt signaling, leading Chairoungdua et al. to investigate a possible link. In cells expressing β-catenin, cotransfection of the tetraspanins CD9 or CD82, but not CD63, decreased the cytoplasmic and nuclear abundance of β-catenin and the activity of a β-catenin transcriptional reporter. The decrease in β-catenin abundance did not occur through degradation by proteasomal or lysosomal pathways and did not require GSK-3β. Instead, the localization of β-catenin changed from nuclear (when a control plasmid or CD63 was cotransfected) to punctate and membrane-associated (when CD9 or CD82 was cotransfected). Electron microscopy revealed that β-catenin was released in exosomes. Besides coexpression of CD9 and CD82, exosomal release of β-catenin required E-cadherin, and CD82 coimmunoprecipitated with β-catenin and E-cadherin in transfected cells. Bone marrow–derived dendritic cells from Cd9–/– knockout mice released fewer exosomes than those from wild-type mice, suggesting a functional role for CD9 in exosome formation. Thus, CD9 and CD82 antagonize β-catenin–dependent signaling by promoting the extracellular release of β-catenin in exosomes.

A. Chairoungdua, D. L. Smith, P. Pochard, M. Hull, M. J. Caplan, Exosome release of β-catenin: A novel mechanism that antagonizes Wnt signaling. J. Cell Biol. 190, 1079–1091 (2010). [Abstract] [Full Text]

Citation: W. Wong, Exit by Exosome. Sci. Signal. 3, ec294 (2010).

To Advertise     Find Products

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