TheDrosophilahomolog of the Exo84 exocyst subunit promotes apical epithelial identity

Abstract

The polarized architecture of epithelial tissues involves a dynamic balance between apical and basolateral membrane domains. Here we show that epithelial polarity in the Drosophila embryo requires the exocyst complex subunit homolog Exo84. Exo84 activity is essential for the apical localization of the Crumbs transmembrane protein, a key determinant of epithelial apical identity. Adherens junction proteins become mislocalized at the cell surface in Exo84 mutants in a pattern characteristic of defects in apical, but not basolateral, components. Loss of Crumbs from the cell surface precedes the disruption of Bazooka and Armadillo localization in Exo84 mutants. Moreover, Exo84 mutants display defects in apical cuticle secretion that are similar to crumbs mutants and are suppressed by a reduction in the basolateral proteins Dlg and Lgl. In Exo84 mutants at advanced stages of epithelial degeneration, apical and adherens junction proteins accumulate in an expanded recycling endosome compartment. These results suggest that epithelial polarity in the Drosophila embryo is actively maintained by exocyst-dependent apical localization of the Crumbs transmembrane protein.

The Garz Sec7 domain guanine nucleotide exchange factor for Arf regulates salivary gland development in Drosophila

“…48,49 The disorganization of Dlg in Garz-depleted organs correlates with disorganization of the actin cytoskeleton and it is likely that both contribute to lack of correct developmental patterning. Dlg interacts genetically with the Exo84 component of the exocyst 66 and thereby may regulate the polarized insertion of newly synthesized membranes that contribute to polarized expansion of cell membranes. Furthermore, the exocyst regulates DE-cadherin traffic from recycling endosomes to the plasma membrane, 67 suggesting that disruption of exocyst function may contribute to decreased levels of surface DE-cadherin.…”

Control of tumourigenesis by the Scribble/Dlg/Lgl polarity module

“…In MDCK epithelial cells, Lgl2 has been shown to interact with syntaxin 4, a component of the basolateral exocyst machinery (Musch et al, 2002). While in Drosophila, the Scribble polarity module has been shown to genetically interact with mutants in a core component of the exocytic machinery, exo84 (Blankenship et al, 2007), which parallels with studies in yeast showing that the Lgl homologues, Sro7 and Sro77, can interact with the exocytic machinery Zhang et al, 2005). Furthermore, Scribble has been shown to have an important role in regulating exocytosis in neuroendocrine cells through its association with the b-Pix-GIT1 complex (Audebert et al, 2004).…”

Membrane Organization and Dynamics in Cell Polarity

“…It is therefore likely that secretion machinery such as the exocyst complex is recruited to specific domains of the plasma membrane for exocytosis. Indeed, the exocyst has been shown to be involved in secretion at both the basolateral and apical domains (Grindstaff et al 1998;Blankenship et al 2007;Oztan et al 2007;Cresawn et al 2007).…”

“…E-cadherin contains sorting signals such as the dileucine motif that control its targeting to the basolateral domain in attached cells at the point of the Golgi complex and recycling endosomes (Miranda et al 2001;Miranda et al 2003). Proper localization of the exocyst in epithelial cells is necessary for the specific delivery of basolateral proteins characteristic of polarized cells, including E-cadherin (Grindstaff et al 1998;Langevin et al 2005); inhibition of exocyst function results in intracellular accumulation of E-cadherin (Langevin et al 2005;Blankenship et al 2007).…”

“…For examples, Rab13 was found to mediate endocytic recycling of occludin, thus regulating tight junction assembly (Terai et al 2008). In Drosophila, mutations in endosomal proteins including Rab5 affect the localization of key polarity determinants such as Crumbs and cause polarity defects and eventually neoplastic tumors (Lu and Bilder 2005); loss of the exocyst component Exo84 resulted in the mislocalization of Crumbs and affected apical identity (Blankenship et al 2007). …”