Abstract
The Drosophila polarity protein Crumbs is essential for the establishment and growth of the apical domain in epithelial cells. The protein Yurt limits the ability of Crumbs to promote apical membrane growth, thereby defining proper apical/lateral membrane ratio that is crucial for forming and maintaining complex epithelial structures such as tubes or acini. Here, we show that Yurt also increases Myosin-dependent cortical tension downstream of Crumbs. Yurt overexpression thus induces apical constriction in epithelial cells. The kinase aPKC phosphorylates Yurt, thereby dislodging the latter from the apical domain and releasing apical tension. In contrast, the kinase Pak1 promotes Yurt dephosphorylation through activation of the phosphatase PP2A. The Pak1–PP2A module thus opposes aPKC function and supports Yurt-induced apical constriction. Hence, the complex interplay between Yurt, aPKC, Pak1, and PP2A contributes to the functional plasticity of Crumbs. Overall, our data increase our understanding of how proteins sustaining epithelial cell polarization and Myosin-dependent cell contractility interact with one another to control epithelial tissue architecture.
Highlights
Simple epithelia form cohesive barriers owing to specialized adherens junctions
APKCCAAX had no effect on apical constriction induced by FLAG167 Yrt5A in which the amino acids targeted by atypical protein kinase C (aPKC) were replaced by non-phosphorylatable alanine 168 residues [(Gamblin et al, 2014); Fig. 4D, E, H]
Expression of membrane-targeted p21-activated kinase 1 (Pak1) [Pak1Myr; (Noren et al, 2000)] suppressed Yrt cortical release induced by aPKC and Par6 (Fig. 7A, B). This result raises the intriguing possibility that Pak1 opposes aPKC function, a premise 215 that we explored by investigating Yrt phosphorylation upon overexpression of these kinases
Summary
Simple epithelia form cohesive barriers owing to specialized adherens junctions. For instance, the cadherin–catenin complex, a major component of the zonula adherens (ZA), links cortical actin filaments of neighboring cells indirectly to ensure strong cell–cell adhesion (Harris and Tepass, 2010). The ability of epithelial cells to support vectorial transport and secretion adjusts the biochemical environment on both sides of the epithelial layer. These unidirectional functions require the polarization of epithelial cells along the apical–basal axis (Laprise and Tepass, 2011). The cytoplasmic tail of Crb contains a PSD95/Dlg1/ZO-1 (PDZ)-domain binding motif (PBM), and a Four point one, Ezrin, Radixin, Moesin (FERM)-domain binding motif (FBM) (Klebes and Knust, 2000; Klose et al, 2013; Pocha and Knust, 2013; Tepass, 2012). The PBM recruits PDZ66 containing proteins such as Stardust (Sdt), which cooperates with Crb in establishing the apical membrane and promoting its growth (Bachmann et al, 2001; Pocha and Knust, 2013; Tepass and Knust, 1993). The FBM interacts with several FERM domain proteins, including Yurt (Yrt)
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