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Cell-cell adhesion is a critical process for the formation and maintenance of tissue patterns during development, as well as invasion and metastasis of cancer cells. Although great strides have been made regarding our understanding of the processes that play a role in cell-cell adhesion, the precise mechanisms by which diverse signaling events regulate cell and tissue architecture is poorly understood. In this commentary we will focus on the Eph/ephrin signaling system, and specifically how the ephrinB1 transmembrane ligand for Eph receptor tyrosine kinases sends signals affecting cell-cell junctions. In a recent study using the epithelial cells of early stage Xenopus embryos, we have shown that loss- or gain-of function of ephrinB1 can disrupt cell-cell contacts and tight junctions. This study reveals a mechanism where ephrinB1 competes with active Cdc42 for binding to Par-6, a scaffold protein central to the Par polarity complex (Par-3/Par-6/Cdc42/aPKC) and disrupts the localization of tight junction-associated proteins (ZO-1, Cingulin) at tight junctions. This competition reduces aPKC activity critical to maintaining and/or forming tight junctions. Finally, phosphorylation of ephrinB1 on specific tyrosine residues can block the interaction between ephrinB1 and Par-6 at tight junctions, and restore tight junction formation. Recent evidence indicates that de-regulation of forward signaling through EphB receptors may play a role in metastatic progression in colon cancer. In light of the new data showing an effect of ephrinB reverse signaling on tight junctions, an additional mechanism can be hypothesized where de-regulation of ephrinB1 expression or phosphorylation may also impact metastatic progression.
Adams,
Roles of ephrinB ligands and EphB receptors in cardiovascular development: demarcation of arterial/venous domains, vascular morphogenesis, and sprouting angiogenesis.
1999, Pubmed
Adams,
Roles of ephrinB ligands and EphB receptors in cardiovascular development: demarcation of arterial/venous domains, vascular morphogenesis, and sprouting angiogenesis.
1999,
Pubmed
Batlle,
EphB receptor activity suppresses colorectal cancer progression.
2005,
Pubmed
Bong,
ephrinB1 signals from the cell surface to the nucleus by recruitment of STAT3.
2007,
Pubmed
,
Xenbase
Brückner,
Tyrosine phosphorylation of transmembrane ligands for Eph receptors.
1997,
Pubmed
Clevers,
EphB/EphrinB receptors and Wnt signaling in colorectal cancer.
2006,
Pubmed
Cortina,
EphB-ephrin-B interactions suppress colorectal cancer progression by compartmentalizing tumor cells.
2007,
Pubmed
Cowan,
The SH2/SH3 adaptor Grb4 transduces B-ephrin reverse signals.
2001,
Pubmed
Cowan,
Vav family GEFs link activated Ephs to endocytosis and axon guidance.
2005,
Pubmed
Davy,
Inhibition of gap junction communication at ectopic Eph/ephrin boundaries underlies craniofrontonasal syndrome.
2006,
Pubmed
Drees,
Alpha-catenin is a molecular switch that binds E-cadherin-beta-catenin and regulates actin-filament assembly.
2005,
Pubmed
Elias,
Gap junction adhesion is necessary for radial migration in the neocortex.
2007,
Pubmed
Georgakopoulos,
Metalloproteinase/Presenilin1 processing of ephrinB regulates EphB-induced Src phosphorylation and signaling.
2006,
Pubmed
Georgiou,
Cdc42, Par6, and aPKC regulate Arp2/3-mediated endocytosis to control local adherens junction stability.
2008,
Pubmed
Harris,
Cdc42 and Par proteins stabilize dynamic adherens junctions in the Drosophila neuroectoderm through regulation of apical endocytosis.
2008,
Pubmed
Himanen,
Repelling class discrimination: ephrin-A5 binds to and activates EphB2 receptor signaling.
2004,
Pubmed
Holland,
Bidirectional signalling through the EPH-family receptor Nuk and its transmembrane ligands.
1996,
Pubmed
Holland,
Juxtamembrane tyrosine residues couple the Eph family receptor EphB2/Nuk to specific SH2 domain proteins in neuronal cells.
1997,
Pubmed
Koshida,
Integrinalpha5-dependent fibronectin accumulation for maintenance of somite boundaries in zebrafish embryos.
2005,
Pubmed
Lee,
Fibroblast growth factor receptor-induced phosphorylation of ephrinB1 modulates its interaction with Dishevelled.
2009,
Pubmed
,
Xenbase
Lee,
EphrinB1 controls cell-cell junctions through the Par polarity complex.
2008,
Pubmed
,
Xenbase
Lee,
Dishevelled mediates ephrinB1 signalling in the eye field through the planar cell polarity pathway.
2006,
Pubmed
,
Xenbase
Leibfried,
Drosophila Cip4 and WASp define a branch of the Cdc42-Par6-aPKC pathway regulating E-cadherin endocytosis.
2008,
Pubmed
Lu,
Ephrin-B reverse signaling is mediated by a novel PDZ-RGS protein and selectively inhibits G protein-coupled chemoattraction.
2001,
Pubmed
,
Xenbase
Mellitzer,
Eph receptors and ephrins restrict cell intermingling and communication.
1999,
Pubmed
Moore,
Morphogenetic movements underlying eye field formation require interactions between the FGF and ephrinB1 signaling pathways.
2004,
Pubmed
,
Xenbase
Ogita,
EphA4-mediated Rho activation via Vsm-RhoGEF expressed specifically in vascular smooth muscle cells.
2003,
Pubmed
Pasquale,
Eph receptor signalling casts a wide net on cell behaviour.
2005,
Pubmed
Penzes,
Rapid induction of dendritic spine morphogenesis by trans-synaptic ephrinB-EphB receptor activation of the Rho-GEF kalirin.
2003,
Pubmed
Perez-Moreno,
Sticky business: orchestrating cellular signals at adherens junctions.
2003,
Pubmed
Poliakov,
Diverse roles of eph receptors and ephrins in the regulation of cell migration and tissue assembly.
2004,
Pubmed
Segura,
Grb4 and GIT1 transduce ephrinB reverse signals modulating spine morphogenesis and synapse formation.
2007,
Pubmed
Shamah,
EphA receptors regulate growth cone dynamics through the novel guanine nucleotide exchange factor ephexin.
2001,
Pubmed
Tanaka,
Association of Dishevelled with Eph tyrosine kinase receptor and ephrin mediates cell repulsion.
2003,
Pubmed
,
Xenbase
Tanaka,
Phosphorylation of ephrin-B1 via the interaction with claudin following cell-cell contact formation.
2005,
Pubmed
Tomita,
Presenilin-dependent intramembrane cleavage of ephrin-B1.
2006,
Pubmed
Wang,
Apical junctional complexes and cell polarity.
2007,
Pubmed
Wimmer-Kleikamp,
Eph-modulated cell morphology, adhesion and motility in carcinogenesis.
2005,
Pubmed
Xu,
Connexin 43-mediated modulation of polarized cell movement and the directional migration of cardiac neural crest cells.
2006,
Pubmed
Xu,
Modulation of mouse neural crest cell motility by N-cadherin and connexin 43 gap junctions.
2001,
Pubmed
Yamada,
Deconstructing the cadherin-catenin-actin complex.
2005,
Pubmed
Yamaguchi,
[Roles of Eph receptors and the cell surface heparan sulfate proteoglycan syndecan-2 in dendritic spine morphogenesis].
2002,
Pubmed
