p120-catenin and β-catenin differentially regulate cadherin adhesive function

Oas, Rebecca G.; Nanes, Benjamin A.; Esimai, Chimdimnma; Vincent, Peter; Garcı́a, Andrés J.; Kowalczyk, Andrew P.

doi:10.1091/mbc.e12-06-0471

Cited by 42 publications

(26 citation statements)

References 41 publications

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“…In addition to regulating cadherin stability, p120 also affects cytoskeletal dynamics through regulation of Rho GTPases (Anastasiadis, 2007; Beckers et al ., 2010). This function is separable from p120 modulation of cadherin endocytosis (Chiasson et al ., 2009), but recruitment of p120 to cell borders can influence the spreading of individual cells on an adhesive substrate (Oas et al ., 2013). Further work is needed to fully understand the connections between adherens junction disassembly and cytoskeletal remodeling in inflammatory conditions and the roles of p120 in both processes.…”

Section: Discussionmentioning

confidence: 99%

p120-catenin regulates VE-cadherin endocytosis and degradation induced by the Kaposi sarcoma–associated ubiquitin ligase K5

Nanes

Grimsley-Myers

Cadwell

et al. 2017

MBoC

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Section: Discussionmentioning

confidence: 99%

p120-catenin regulates VE-cadherin endocytosis and degradation induced by the Kaposi sarcoma–associated ubiquitin ligase K5

Nanes

Grimsley-Myers

Cadwell

et al. 2017

MBoC

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“…However, only one isoform is expressed in the vascular endothelium: the classical cadherin, VE-cadherin. Like other classical cadherins, VE-cadherin exhibits (1) an extracellular amino-terminus that can multimerize and interact in trans with other cadherin molecules expressed on adjacent cells, (2) a single-pass transmembrane domain and (3) a cytoplasmic carboxyl-terminus that binds to β-catenin and p120 catenin [6,7]. In turn, β-catenin recruits α-catenin, which functions to control binding to and bundling of actin filaments that strengthen adhesion [8].…”

Section: Introductionmentioning

confidence: 99%

Phosphoregulation of the C. elegans cadherin–catenin complex

Callaci

Morrison

Shao

et al. 2015

Biochemical Journal

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Adherens junctions play key roles in mediating cell–cell contacts during tissue development. In Caenorhabditis elegans embryos, the cadherin–catenin complex (CCC), composed of the classical cadherin HMR-1 and members of three catenin families, HMP-1, HMP-2 and JAC-1, is necessary for normal blastomere adhesion, gastrulation, ventral enclosure of the epidermis and embryo elongation. Disruption of CCC assembly or function results in embryonic lethality. Previous work suggests that components of the CCC are subject to phosphorylation. However, the identity of phosphorylated residues in CCC components and their contributions to CCC stability and function in a living organism remain speculative. Using mass spectrometry, we systematically identify phosphorylated residues in the essential CCC subunits HMR-1, HMP-1 and HMP-2 in vivo. We demonstrate that HMR-1/cadherin phosphorylation occurs on three sites within its β-catenin binding domain that each contributes to CCC assembly on lipid bilayers. In contrast, phosphorylation of HMP-2/β-catenin inhibits its association with HMR-1/cadherin in vitro, suggesting a role in CCC disassembly. Although HMP-1/α-catenin is also phosphorylated in vivo, phosphomimetic mutations do not affect its ability to associate with other CCC components or interact with actin in vitro. Collectively, our findings support a model in which distinct phosphorylation events contribute to rapid CCC assembly and disassembly, both of which are essential for morphogenetic rearrangements during development.

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“…␤-Catenin binds to the catenin-binding domain of the cadherin cytoplasmic tail. Through interactions between ␤-and ␣-catenin, the cadherin is linked to the actin cytoskeleton, which increases the adhesive strength of the junction (11)(12)(13)(14)(15).…”

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confidence: 99%

Ankyrin-G Inhibits Endocytosis of Cadherin Dimers

Cadwell¹,

Jenkins

Bennett

et al. 2016

Journal of Biological Chemistry

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Dynamic regulation of endothelial cell adhesion is central to vascular development and maintenance. Furthermore, altered endothelial adhesion is implicated in numerous diseases. Therefore, normal vascular patterning and maintenance require tight regulation of endothelial cell adhesion dynamics. However, the mechanisms that control junctional plasticity are not fully understood. Vascular endothelial cadherin (VE-cadherin) is an adhesive protein found in adherens junctions of endothelial cells. VE-cadherin mediates adhesion through trans interactions formed by its extracellular domain. Trans binding is followed by cis interactions that laterally cluster the cadherin in junctions. VE-cadherin is linked to the actin cytoskeleton through cytoplasmic interactions with ␤-and ␣-catenin, which serve to increase adhesive strength. Furthermore, p120-catenin binds to the cytoplasmic tail of cadherin and stabilizes it at the plasma membrane. Here we report that induced cis dimerization of VE-cadherin inhibits endocytosis independent of both p120 binding and trans interactions. However, we find that ankyrin-G, a protein that links membrane proteins to the spectrin-actin cytoskeleton, associates with VE-cadherin and inhibits its endocytosis. Ankyrin-G inhibits VE-cadherin endocytosis independent of p120 binding. We propose a model in which ankyrin-G associates with and inhibits the endocytosis of VEcadherin cis dimers. Our findings support a novel mechanism for regulation of VE-cadherin endocytosis through ankyrin association with cadherin engaged in lateral interactions.

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p120-catenin and β-catenin differentially regulate cadherin adhesive function

Abstract: β-Catenin and p120-catenin bind to cadherin cytoplasmic tails and are believed to modulate cadherin function and adhesion. This study shows that p120-catenin and β-catenin function in a distinct but complementary manner to regulate the size and strength of cadherin adhesive contacts.

Cited by 42 publications

References 41 publications

p120-catenin regulates VE-cadherin endocytosis and degradation induced by the Kaposi sarcoma–associated ubiquitin ligase K5

p120-catenin regulates VE-cadherin endocytosis and degradation induced by the Kaposi sarcoma–associated ubiquitin ligase K5

Phosphoregulation of the C. elegans cadherin–catenin complex

Ankyrin-G Inhibits Endocytosis of Cadherin Dimers

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