Qin, Y. , Capaldo, C. , Gumbiner, B.M. & Macara, I.G. The mammalian Scribble polarity protein regulates epithelial cell adhesion and migration through E-cadherin. J. Cell Biol. 171, 1061-1071

Center for Cell Signaling, Department of Microbiology, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.
The Journal of Cell Biology (Impact Factor: 9.83). 01/2006; 171(6):1061-71. DOI: 10.1083/jcb.200506094
Source: PubMed


Scribble (Scrib) is a conserved polarity protein required in Drosophila melanogaster for synaptic function, neuroblast differentiation, and epithelial polarization. It is also a tumor suppressor. In rodents, Scrib has been implicated in receptor recycling and planar polarity but not in apical/basal polarity. We now show that knockdown of Scrib disrupts adhesion between Madin-Darby canine kidney epithelial cells. As a consequence, the cells acquire a mesenchymal appearance, migrate more rapidly, and lose directionality. Although tight junction assembly is delayed, confluent monolayers remain polarized. These effects are independent of Rac activation or Scrib binding to betaPIX. Rather, Scrib depletion disrupts E-cadherin-mediated cell-cell adhesion. The changes in morphology and migration are phenocopied by E-cadherin knockdown. Adhesion is partially rescued by expression of an E-cadherin-alpha-catenin fusion protein but not by E-cadherin-green fluorescent protein. These results suggest that Scrib stabilizes the coupling between E-cadherin and the catenins and are consistent with the idea that mammalian Scrib could behave as a tumor suppressor by regulating epithelial cell adhesion and migration.

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Article: Qin, Y. , Capaldo, C. , Gumbiner, B.M. & Macara, I.G. The mammalian Scribble polarity protein regulates epithelial cell adhesion and migration through E-cadherin. J. Cell Biol. 171, 1061-1071

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    • "Scrib localization at the basolateral membrane is dependent on cell–cell adhesion mediated by E-cadherin.28 In return, the Scrib complex is necessary to maintain E-cadherin-mediated adhesions, and specifies the basolateral membrane.29 Furthermore the Scrib complex opposes apical membrane identity and in Drosophila, expression of Scrib mutants cause the delocalization of apical proteins to all cell surfaces.30 "
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    • "scrib has been shown to act as a neoplastic tumor suppressor (Bilder, 2004; Bilder et al., 2000; Bilder and Perrimon, 2000) and scrib-deficient follicular cells exhibit mislocalization of basolateral junction proteins such as E-cadherin (Zhao et al., 2008). Scrib-depleted MDCK cells were less adherent apparently due to compromised E-cadherin function (Qin et al., 2005). Analysis of the mouse mutant, Crc, which expresses a truncated form of Scrib in which the last two PDZ domains are absent (Murdoch et al., 2003), has shown that Scrib is essential for planar cell polarity (Montcouquiol et al., 2003), for maintaining epithelial cohesion during lung development (Yates et al., 2013) and for angiogenesis (Michaelis et al., 2013). "
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