RRC ID 6259
Author Phua DC, Humbert PO, Hunziker W.
Title Vimentin regulates scribble activity by protecting it from proteasomal degradation.
Journal Mol. Biol. Cell
Abstract 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.
Volume 20(12)
Pages 2841-55
Published 2009-6
DOI 10.1091/mbc.e08-02-0199
PII E08-02-0199
PMID 19386766
PMC PMC2695792
MeSH Animals Cell Aggregation Cell Line Cell Movement Cell Shape Dogs Endothelial Cells / metabolism Gene Silencing Humans Intermediate Filaments / metabolism Membrane Proteins / chemistry Membrane Proteins / metabolism* Proteasome Endopeptidase Complex / metabolism* Protein Binding Protein Processing, Post-Translational* Protein Stability Protein Structure, Tertiary Protein Transport Rats Tumor Suppressor Proteins / chemistry Tumor Suppressor Proteins / metabolism* Umbilical Veins / cytology Vimentin / metabolism* Wound Healing
IF 3.905
Times Cited 28
Zebrafish ?