Robust Asymmetric Localization of Planar Polarity Proteins Is Associated with Organization into Signalosome-like Domains of Variable Stoichiometry

Strutt, Helen; Gamage, Jessica; Strutt, David

doi:10.1016/j.celrep.2016.11.021

Cited by 50 publications

(100 citation statements)

References 50 publications

(107 reference statements)

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“…an approached well-established in various models due to linear scaling of EGFP signal with the amount of protein present [63,64]. E-cad-GFP localized asymmetrically at this stage with a 1:2 (AP:DV) ratio between the two cell borders ( Fig.…”

Section: Both Loss and Overexpression Of P120ctn Stabilize E-cadherinmentioning

confidence: 52%

“…where F im is a size of the immobile fraction, T fast and T slow are the half times, and CLC-GFP puncta: Images were analysed using a custom script in MATLAB described in [64]. This was modified for unpaired data by calculating a threshold value for puncta detection using a mean calculated from all of the control images and applying this threshold to the experimental images.…”

Section: Data Processing and Statistical Analysismentioning

confidence: 99%

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E-cadherin endocytosis is modulated by p120-catenin through the opposing actions of RhoA and Arf1

Greig

Bulgakova

2018

Preprint

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The regulation of E-cadherin at the plasma membrane by endocytosis is of vital importance for developmental and disease. p120-catenin, which binds to the E-cadherin C-terminus, can both promote and inhibit E-cadherin endocytosis. However, little is known about what determines the directionality of p120-catenin activity, and the molecules downstream. Here, we have discovered that p120-catenin fine-tunes the clathrin-mediated endocytosis of Ecadherin in Drosophila embryonic epidermal cells. It simultaneously activated two actinremodelling pathways with opposing effects: RhoA, which stabilized E-cadherin at the membrane, and Arf1, which promoted internalization. Epistasis experiments revealed that RhoA additionally inhibited Arf1. E-cadherin was efficiently endocytosed only in the presence of intermediate p120-catenin amounts with too little and too much p120-catenin inhibiting E-cadherin endocytosis. Finally, we found that p120-catenin levels altered the tension of the plasma membrane. Altogether, this shows that p120-catenin is a central hub which co-ordinates cell adhesion, endocytosis, and actin dynamics with tissue tension.requires Rho-kinase for recruitment to AJs [76][77][78].

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Section: Both Loss and Overexpression Of P120ctn Stabilize E-cadherinmentioning

confidence: 52%

Section: Data Processing and Statistical Analysismentioning

confidence: 99%

E-cadherin endocytosis is modulated by p120-catenin through the opposing actions of RhoA and Arf1

Greig

Bulgakova

2018

Preprint

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“…Though the importance of asymmetric expression of PCP proteins in the plane is well established in both Drosophila 22 and vertebrates 23 , little is known regarding their apical restriction. To test the significance of VANGL2 expression and localization, we generated transgenic mouse lines in which Cre-mediated recombination inactivates β-actin promoter-driven GFP expression and induces expression of a Cherry-VANGL2 fusion protein (Fig.…”

Section: Resultsmentioning

confidence: 99%

Apical restriction of the planar cell polarity component VANGL in pancreatic ducts is required to maintain epithelial integrity

Flasse

Yennek

Cortijo

et al. 2019

Preprint

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15Cell polarity is essential for the architecture and function of numerous epithelial tissues. Here we show 16 how planar cell polarity (PCP), so far studied principally in flat epithelia, is deployed during the 17 morphogenesis of a tubular organ. Using the mammalian pancreas as a model, we report that 18 components of the core PCP pathway such as the transmembrane protein Van Gogh-like (VANGL), are 19 progressively apically-restricted. VANGL expression becomes asymmetrically localized at the apical 20 surface of ductal cells, revealing a planar polarization of the pancreatic duct. We further show that 21 restricting VANGL to these discrete sites of expression is crucial for epithelial integrity. Expansion of 22 expression on basolateral membranes of the progenitors leads to their death and extrusion from the 23 epithelium, as previously observed for perturbations of apico-basal polarity. Using organoids and in vivo 24 analyses, we show that cell elimination is induced by a decrease of Rock activity via Dishevelled. 25 2 group of six families of proteins is required to coordinate planar polarization between neighboring cells: 38 the transmembrane proteins Frizzled (vertebrate: FZD; fly: FZ), CELSR (CELSR; FMI) and Van Gogh-like 39 (VANGL; STBM/VANG) and the cytosolic-submembrane proteins Dishevelled (DVL; DSH), 40Inversin/Diversin (INV/ANKRD6; DGO), and Prickle (PK). The PCP signaling system employs intra-and inter-41 cellular feedback interactions between its core components to establish their characteristic asymmetric 42 cellular distributions. In the most comprehensively-characterized system, the Drosophila wing blade, the 43 FZ-DSH-DGO complex localizes to intercellular junctions facing the VANG-PK complex in the adjacent 44 cell. FMI, an atypical cadherin, localizes to both sides of the apical junction and bridges the FZ and VANG 45 complexes between neighboring cells. These intercellular interactions are counterbalanced 46 intracellularly by reciprocal inhibitory interactions between the two complexes 1,2 . 47While traditionally depicted in flat epithelia that require directional motion or an oriented structure, it is less 48 clear how these proteins are organized or function in complex epithelia forming tubular structures 3 . The 49 developing pancreas consists of a network of tubes lined by polarized progenitors, the apical membranes of 50 which line the duct lumen 4,5 . This network is dynamic and remodeled throughout development while the 51 pancreatic epithelium grows and progenitors commit to various specialized fates 6 . At embryonic day 52 E10.5, multipotent progenitors are organized around discrete micro-lumens 7,8 . By E12.5, these micro-53 lumens have fused to form a mesh of interconnected ducts. Distal "Tip" progenitors committed to an 54 exocrine fate are restricted to the periphery while the core of this plexus contains bipotent "Trunk" 55 progenitors that subsequently either remain in the epithelium to form mature duct cells or delaminate 56 to give rise to endocrine cells. By birth, the duc...

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“…Another explanation could relate to some direct effect of Pk (and Sple) on Vang (Bastock et al, 2003) which fits our observations with clones overexpressing Pk (Figure 7). The function of Vang in the Stan system is somewhat unclear; like Pk, Vang is present in larger than stoichiometric amounts in relation to the two molecules that form the intercellular bridge, Stan and Fz (Strutt et al, 2016), yet affects bridge function (Struhl et al, 2012). The abdominal phenotypes of Vang - and pk-sple - are somewhat similar, both having areas of reversed polarity (Lawrence et al, 2004), suggesting a commonality of function.…”

Section: Discussionmentioning

confidence: 99%

Planar cell polarity: thepricklegene acts independently on both the Ds/Ft and the Stan Systems

Casal

Ibanez-Jimenez

Lawrence

2017

Preprint

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Epithelial cells are polarised within the plane of the epithelium, forming oriented structures whose coordinated and consistent polarity (planar cell polarity, PCP) relates to the principal axes of the body or organ. In Drosophila at least two separate molecular systems generate and interpret intercellular polarity signals: Dachsous/Fat, and the “core” or Stan system. Here we study the prickle gene and its protein products Prickle and Spiny leg. Much research on PCP has focused on the asymmetric localisation of core proteins in the cell and as a result prickle was placed in the heart of the Stan system. Here we ask if this view is correct and how the prickle gene relates to the two systems. We find that prickle can affect, separately, both systems — however, neither Pk nor Sple are essential components of the Ds/Ft or the Stan system, nor do they act as a functional link between the two systems.

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Robust Asymmetric Localization of Planar Polarity Proteins Is Associated with Organization into Signalosome-like Domains of Variable Stoichiometry

Cited by 50 publications

References 50 publications

E-cadherin endocytosis is modulated by p120-catenin through the opposing actions of RhoA and Arf1

E-cadherin endocytosis is modulated by p120-catenin through the opposing actions of RhoA and Arf1

Apical restriction of the planar cell polarity component VANGL in pancreatic ducts is required to maintain epithelial integrity

Planar cell polarity: thepricklegene acts independently on both the Ds/Ft and the Stan Systems

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