Interaction of scribble with Zonula Occludens and Intermediate filament proteins

Abstract

Cell polarization - the asymmetric distribution of cellular components into functionally separate regions - is fundamental to processes such as proliferation and movement. The multidomain protein Scribble (Scrib) is a key polarity regulator and neoplastic tumor suppressor in Drosophila. Mammalian Scrib is implicated in epithelial cell - cell adhesion and polarization during directed cell migration. In this study, we characterize a novel interaction between Scrib and the tight junction proteins Zonula Occludens (ZO) -2 and -3; and the intermediate filament vimentin. In fibroblasts, ZO-2 and -3 interactions with Scrib are responsible for its recruitment to vesicular structures, possibly reflecting a spatio-temporal role of these ZO proteins in the recruitment of Scrib during epithelial cell polarization. Vimentin interaction has a stabilizing effect on Scrib levels. Vimentin depletion results in the proteasome-dependent degradation of Scrib, which consequently leads to defective epithelial cell - cell adhesion and deregulated cell migration, closely phenocopying Scrib depletion. The findings imply a possible regulatory function for vimentin in Scrib homeostasis during epithelial migration.