2.50
Hdl Handle:
http://hdl.handle.net/10033/620136
Title:
p120 Catenin-Mediated Stabilization of E-Cadherin Is Essential for Primitive Endoderm Specification.
Authors:
Pieters, Tim; Goossens, Steven; Haenebalcke, Lieven; Andries, Vanessa; Stryjewska, Agata; De Rycke, Riet; Lemeire, Kelly; Hochepied, Tino; Huylebroeck, Danny; Berx, Geert; Stemmler, Marc P; Wirth, Dagmar ( 0000-0002-2541-6251 ) ; Haigh, Jody J; van Hengel, Jolanda; van Roy, Frans
Abstract:
E-cadherin-mediated cell-cell adhesion is critical for naive pluripotency of cultured mouse embryonic stem cells (mESCs). E-cadherin-depleted mESC fail to downregulate their pluripotency program and are unable to initiate lineage commitment. To further explore the roles of cell adhesion molecules during mESC differentiation, we focused on p120 catenin (p120ctn). Although one key function of p120ctn is to stabilize and regulate cadherin-mediated cell-cell adhesion, it has many additional functions, including regulation of transcription and Rho GTPase activity. Here, we investigated the role of mouse p120ctn in early embryogenesis, mESC pluripotency and early fate determination. In contrast to the E-cadherin-null phenotype, p120ctn-null mESCs remained pluripotent, but their in vitro differentiation was incomplete. In particular, they failed to form cystic embryoid bodies and showed defects in primitive endoderm formation. To pinpoint the underlying mechanism, we undertook a structure-function approach. Rescue of p120ctn-null mESCs with different p120ctn wild-type and mutant expression constructs revealed that the long N-terminal domain of p120ctn and its regulatory domain for RhoA were dispensable, whereas its armadillo domain and interaction with E-cadherin were crucial for primitive endoderm formation. We conclude that p120ctn is not only an adaptor and regulator of E-cadherin, but is also indispensable for proper lineage commitment.
Affiliation:
Helmholtz Centre for infection researchz, Inhoffenstr. 7, 38124 Braunschweig.
Citation:
p120 Catenin-Mediated Stabilization of E-Cadherin Is Essential for Primitive Endoderm Specification. 2016, 12 (8):e1006243 PLoS Genet.
Journal:
PLoS genetics
Issue Date:
Aug-2016
URI:
http://hdl.handle.net/10033/620136
DOI:
10.1371/journal.pgen.1006243
PubMed ID:
27556156
Type:
Article
Language:
en
ISSN:
1553-7404
Appears in Collections:
publications of the research group modell systems for infections and immunity (MSYS)

Full metadata record

DC FieldValue Language
dc.contributor.authorPieters, Timen
dc.contributor.authorGoossens, Stevenen
dc.contributor.authorHaenebalcke, Lievenen
dc.contributor.authorAndries, Vanessaen
dc.contributor.authorStryjewska, Agataen
dc.contributor.authorDe Rycke, Rieten
dc.contributor.authorLemeire, Kellyen
dc.contributor.authorHochepied, Tinoen
dc.contributor.authorHuylebroeck, Dannyen
dc.contributor.authorBerx, Geerten
dc.contributor.authorStemmler, Marc Pen
dc.contributor.authorWirth, Dagmaren
dc.contributor.authorHaigh, Jody Jen
dc.contributor.authorvan Hengel, Jolandaen
dc.contributor.authorvan Roy, Fransen
dc.date.accessioned2016-09-14T11:42:11Z-
dc.date.available2016-09-14T11:42:11Z-
dc.date.issued2016-08-
dc.identifier.citationp120 Catenin-Mediated Stabilization of E-Cadherin Is Essential for Primitive Endoderm Specification. 2016, 12 (8):e1006243 PLoS Genet.en
dc.identifier.issn1553-7404-
dc.identifier.pmid27556156-
dc.identifier.doi10.1371/journal.pgen.1006243-
dc.identifier.urihttp://hdl.handle.net/10033/620136-
dc.description.abstractE-cadherin-mediated cell-cell adhesion is critical for naive pluripotency of cultured mouse embryonic stem cells (mESCs). E-cadherin-depleted mESC fail to downregulate their pluripotency program and are unable to initiate lineage commitment. To further explore the roles of cell adhesion molecules during mESC differentiation, we focused on p120 catenin (p120ctn). Although one key function of p120ctn is to stabilize and regulate cadherin-mediated cell-cell adhesion, it has many additional functions, including regulation of transcription and Rho GTPase activity. Here, we investigated the role of mouse p120ctn in early embryogenesis, mESC pluripotency and early fate determination. In contrast to the E-cadherin-null phenotype, p120ctn-null mESCs remained pluripotent, but their in vitro differentiation was incomplete. In particular, they failed to form cystic embryoid bodies and showed defects in primitive endoderm formation. To pinpoint the underlying mechanism, we undertook a structure-function approach. Rescue of p120ctn-null mESCs with different p120ctn wild-type and mutant expression constructs revealed that the long N-terminal domain of p120ctn and its regulatory domain for RhoA were dispensable, whereas its armadillo domain and interaction with E-cadherin were crucial for primitive endoderm formation. We conclude that p120ctn is not only an adaptor and regulator of E-cadherin, but is also indispensable for proper lineage commitment.en
dc.language.isoenen
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.titlep120 Catenin-Mediated Stabilization of E-Cadherin Is Essential for Primitive Endoderm Specification.en
dc.typeArticleen
dc.contributor.departmentHelmholtz Centre for infection researchz, Inhoffenstr. 7, 38124 Braunschweig.en
dc.identifier.journalPLoS geneticsen

Related articles on PubMed

This item is licensed under a Creative Commons License
Creative Commons
All Items in HZI are protected by copyright, with all rights reserved, unless otherwise indicated.