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Vol. 20, Issue 12, 2841-2855, June 15, 2009

This Article Full Text Full Text (PDF) Supplemental Materials All Versions of this Article: E08-02-0199v1 20/12/2841    most recent Alert me when this article is cited Alert me if a correction is posted Services Related articles in Mol. Biol. Cell Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Phua, D. C.Y. Articles by Hunziker, W. Search for Related Content PubMed PubMed Citation Articles by Phua, D. C.Y. Articles by Hunziker, W.

Vimentin Regulates Scribble Activity by Protecting It from Proteasomal Degradation

Dominic C.Y. Phua^*, Patrick O. Humbert, and Walter Hunziker^*

*Epithelial Cell Biology Laboratory, Cancer and Developmental Cell Biology Division, Institute of Molecular and Cell Biology, Agency for Science, Technology and Research, Singapore 138673, Republic of Singapore; and Cell Cycle and Cancer Genetics Laboratory, Peter MacCallum Cancer Centre, Melbourne 8006, Victoria, Australia

Submitted February 25, 2008; Revised March 17, 2009; Accepted April 13, 2009
Monitoring Editor: M. Bishr Omary

InCytes from MBC

Scribble (Scrib), Discs large, and Lethal giant larvae form a protein complex that regulates different aspects of cell polarization, including apical–basal asymmetry in epithelial cells and anterior–posterior polarity in migrating cells. Here, we show that Scrib interacts with the intermediate filament cytoskeleton in epithelial Madin-Darby canine kidney (MDCK) cells and endothelial human umbilical vein endothelial cells. Scrib binds vimentin via its postsynaptic density 95/disc-large/zona occludens domains and in MDCK cells redistributes from filaments to the plasma membrane during the establishment of cell–cell contacts. RNA interference-mediated silencing of Scrib, vimentin, or both in MDCK cells results in defects in the polarization of the Golgi apparatus during cell migration. Concomitantly, wound healing is delayed due to the loss of directional movement. Furthermore, cell aggregation is dependent on both Scrib and vimentin. The similar phenotypes observed after silencing either Scrib or vimentin support a coordinated role for the two proteins in cell migration and aggregation. Interestingly, silencing of vimentin leads to an increased proteasomal degradation of Scrib. Thus, the upregulation of vimentin expression during epithelial to mesenchymal transitions may stabilize Scrib to promote directed cell migration.

Address correspondence to: Walter Hunziker (hunziker{at}imcb.a-star.edu.sg)

Abbreviations used: AJ, adherens junction; Dlg, Discs large; IF, intermediate filament; Lgl, Lethal giant larvae; PCR, polymerase chain reaction; PDZ, postsynaptic density 95/disc-large/zona occludens; Scrib, Scribble; siRNA, small interfering RNA; WT, wild-type; ZO, zonula occludens.

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