Rap1 acts via multiple mechanisms to position Canoe and adherens junctions and mediate apical-basal polarity establishment

Citations Over TimeTop 10% of 2017 papers

Abstract

Epithelial apical-basal polarity drives assembly and function of most animal tissues. Polarity initiation requires cell-cell adherens junction assembly at the apical-basolateral boundary. Defining the mechanisms underlying polarity establishment remains a key issue. Drosophila embryos provide an ideal model, as 6000 polarized cells assemble simultaneously. Current data place the actin-junctional linker Canoe (fly homolog of Afadin) at the top of the polarity hierarchy, where it directs Bazooka/Par3 and adherens junction positioning. Here we define mechanisms regulating Canoe localization/function. Spatial organization of Canoe is multifaceted, involving membrane localization, recruitment to nascent junctions and macromolecular assembly at tricellular junctions. Our data suggest apical activation of the small GTPase Rap1 regulates all three events, but support multiple modes of regulation. The Rap1GEF Dizzy (PDZ-GEF) is crucial for Canoe tricellular junction enrichment but not apical retention. The Rap1-interacting RA domains of Canoe mediate adherens junction and tricellular junction recruitment but are dispensable for membrane localization. Our data also support a role for Canoe multimerization. These multifactorial inputs shape Canoe localization, correct Bazooka and adherens junction positioning, and thus apical-basal polarity. We integrate the existing data into a new polarity establishment model.

Related Papers

• → Dynamics of adherens junctions in epithelial establishment, maintenance, and remodeling(2011)488 cited
• → Depletion of protein kinase N3 (PKN3) impairs actin and adherens junctions dynamics and attenuates endothelial cell activation(2012)24 cited
• → Adducins regulate remodeling of intercellular junctions in model human epithelia(2010)1 cited
• → Scribble and Discs-large direct adherens junction positioning and supermolecular assembly to establish apical-basal polarity(2019)1 cited
• The study on the adhesion and motility of endothelial cells derived from embryonic stem cells : 胚性幹細胞由来内皮細胞における接着と運動に関する研究; ハイセイ カンサイボウ ユライ ナイヒ サイボウ ニ オケル セッチャク ト ウンドウ ニ カンスル ケンキュウ(2020)