Shroom3-mediated recruitment of Rho kinases to the apical cell junctions regulates epithelial and neuroepithelial planar remodeling

Abstract

Remodeling of epithelial sheets plays important roles in animal morphogenesis. Shroom3 is known to regulate the apical constriction of epithelial cells. Here, we show that Shroom3 binds ROCKs and recruits them to the epithelial apical junctions. We identified the Shroom3-binding site (RII-C1) on ROCKs, and found that RII-C1 could antagonize the Shroom3-ROCK interaction, interfering with the action of Shroom3 on cell morphology. In the invaginating neural plate/tube, Shroom3 colocalized with ROCKs at the apical junctions; Shroom3 depletion or RII-C1 expression in the tube removed these apically localized ROCKs, and concomitantly blocked neural tube closure. Closing neural plate exhibited peculiar cell assemblies, including rosette formation, as well as a planar-polarized distribution of phosphorylated myosin regulatory light chain, but these were abolished by ROCK inhibition or RII-C1 expression. These results demonstrate that the Shroom3-ROCK interaction is crucial for the regulation of epithelial and neuroepithelial cell arrangement and remodeling.

Folate receptor 1 is necessary for neural plate cell apical constriction during Xenopus neural tube formation

“…We find Folr1 colocalized at the apical membrane of superficial neural plate cells with C-cadherin and β-catenin. Apically localized molecules play crucial roles during neural plate folding as scaffolding proteins that participate in the apical constriction of cells (Eom et al, 2011;Haigo et al, 2003;Hildebrand and Soriano, 1999;Morita et al, 2010;Nandadasa et al, 2009;Nishimura and Takeichi, 2008;Ossipova et al, 2014). For example, cadherins coordinate the cytoskeletal dynamics and cell-cell interactions necessary for tissue bending and morphogenesis (Nishimura and Takeichi, 2009;West and Harris, 2016).…”

Adherens Junction: Molecular Architecture and Regulation

“…A well-known example is the Shroom3-dependent constriction of the zonula adherens (ZA) in epithelial layers, where constriction plays an important role in epithelial folding or bending (Haigo et al 2003;Hildebrand 2005). In this case, the actin-binding protein Shroom3 recruits Rho kinases (ROCKs) near the ZA, and activates myosin-II, inducing the contraction of the circumferential actin belts (Nishimura and Takeichi 2008). The actomyosin-dependent regulation of the AJ is also implicated in cell intercalation during early morphogenesis of Drosophila embryos (Bertet et al 2004;Zallen and Wieschaus 2004;Blankenship et al 2006).…”

Spatial integration of E-cadherin adhesion, signalling and the epithelial cytoskeleton

“…The mechanisms involved are unclear, but may involve the ability of p120 CTN bound to cadherin complexes to localise ROCK at cell-cell contacts [61]. The latter may or may not involve the ROCK partner Shroom3 [62,63], a known regulator of epithelial apical contraction [64]. In endothelial cells and C.elegans, p120 CTN may also dynamically modulate contractility at the lateral domains via its interaction with RhoA upstream regulators [65,66].…”