Non-canonical Wnt signaling induces ubiquitination and degradation of Syndecan4

Loreto Carvallo, Rosana Muñoz, Francisco Bustos, Noelia Escobedo, Héctor Carrasco, Gonzalo Olivares, Juan Larraín

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

Dynamic regulation of cell adhesion receptors is required for proper cell migration in embryogenesis, tissue repair, and cancer. Integrins and Syndecan4 (SDC4) are the main cell adhesion receptors involved in focal adhesion formation and are required for cell migration. SDC4 interacts biochemically and functionally with components of the Wnt pathway such as Frizzled7 and Dishevelled. Non-canonical Wnt signaling, particularly components of the planar cell polarity branch, controls cell adhesion and migration in embryogenesis and metastasic events. Here, we evaluate the effect of this pathway on SDC4. We have found that Wnt5a reduces cell surface levels and promotes ubiquitination and degradation of SDC4 in cell lines and dorsal mesodermal cells from Xenopus gastrulae. Gain- and loss-of-function experiments demonstrate that Dsh plays a key role in regulating SDC4 steady-state levels. Moreover, a SDC4 deletion construct that interacts inefficiently with Dsh is resistant to Wnt5a-induced degradation. Non-canonical Wnt signaling promotes monoubiquitination of the variable region of SDC4 cytoplasmic domain. Mutation of these specific residues abrogates ubiquitination and results in increased SDC4 steady state levels. This is the first example of a cell surface protein ubiquitinated and degraded in a Wnt/Dsh-dependent manner.

Original languageEnglish (US)
Pages (from-to)29546-29555
Number of pages10
JournalJournal of Biological Chemistry
Volume285
Issue number38
DOIs
StatePublished - Sep 17 2010

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Carvallo, L., Muñoz, R., Bustos, F., Escobedo, N., Carrasco, H., Olivares, G., & Larraín, J. (2010). Non-canonical Wnt signaling induces ubiquitination and degradation of Syndecan4. Journal of Biological Chemistry, 285(38), 29546-29555. https://doi.org/10.1074/jbc.M110.155812