Interaction of Junctional Adhesion Molecule with the Tight Junction Components ZO-1, Cingulin, and Occludin

Bazzoni, Gianfranco; Martínez-Estrada, Ofelia M.; Orsenigo, Fabrizio; Cordenonsi, Michelangelo; Citi, Sandra; Dejana, Elisabetta

doi:10.1074/jbc.m905251199

Cited by 434 publications

(326 citation statements)

References 53 publications

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“…Previous reports suggest that the PDZ binding motif of JAM-A is necessary for its function (Bazzoni et al, 2000;Ebnet et al, 2001;Severson et al, 2008), and this presumably requires JAM-A interactions with PDZ domain-containing scaffolding proteins. To identify scaffolding proteins that mediate JAM-A function, we focused on the candidate proteins Afadin and ZO-1, which have previously been reported to associate with JAM-A (Ebnet et al, 2000;Fukuhara et al, 2002).…”

Section: Jam-a Regulates Epithelial Cell Migration Through Afadin Butmentioning

confidence: 99%

Junctional Adhesion Molecule A Interacts with Afadin and PDZ-GEF2 to Activate Rap1A, Regulate β1 Integrin Levels, and Enhance Cell Migration

Severson

Lee

Capaldo

et al. 2009

MBoC

160

166

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Junctional adhesion molecule-A (JAM-A) is a transmembrane tight junction protein that has been shown to regulate barrier function and cell migration through incompletely understood mechanisms. We have previously demonstrated that JAM-A regulates cell migration by dimerization of the membrane-distal immunoglobulin-like loop and a C-terminal postsynaptic density 95/disc-large/zona occludens (PDZ) binding motif. Disruption of dimerization resulted in decreased epithelial cell migration secondary to diminished levels of ␤1 integrin and active Rap1. Here, we report that JAM-A is physically and functionally associated with the PDZ domain-containing molecules Afadin and PDZ-guanine nucleotide exchange factor (GEF) 2, but not zonula occludens (ZO)-1, in epithelial cells, and these interactions mediate outside-in signaling events. Both Afadin and PDZ-GEF2 colocalized and coimmunoprecipitated with JAM-A. Furthermore, association of PDZ-GEF2 with Afadin was dependent on the expression of JAM-A. Loss of JAM-A, Afadin, or PDZ-GEF2, but not ZO-1 or PDZ-GEF1, similarly decreased cellular levels of activated Rap1, ␤1 integrin protein, and epithelial cell migration. The functional effects observed were secondary to decreased levels of Rap1A because knockdown of Rap1A, but not Rap1B, resulted in decreased ␤1 integrin levels and reduced cell migration. These findings suggest that JAM-A dimerization facilitates formation of a complex with Afadin and PDZ-GEF2 that activates Rap1A, which regulates ␤1 integrin levels and cell migration.

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Section: Jam-a Regulates Epithelial Cell Migration Through Afadin Butmentioning

confidence: 99%

Junctional Adhesion Molecule A Interacts with Afadin and PDZ-GEF2 to Activate Rap1A, Regulate β1 Integrin Levels, and Enhance Cell Migration

Severson

Lee

Capaldo

et al. 2009

MBoC

160

166

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“…Four JAMs -JAM-A, -B, -C and -D -have been identified, and all four can mediate homotypic cell-cell adhesion. Several of the JAM proteins, as well as the related proteins coxsackievirus and adenovirus receptor (CAR), CAR-like membrane protein (CLMP) and the endothelial-cellselective adhesion molecule (ESAM), associate with TJs and interact with adaptor proteins of the cytoplasmic plaque (Bazzoni et al, 2000;Ebnet et al, 2003;Ebnet et al, 2000;Raschperger et al, 2004;Wegmann et al, 2004). JAMs regulate adhesion between leukocytes and endothelial cells, as well as the paracellular transmigration of leukocytes across the endothelium, and have been shown to regulate the development of cell polarity by binding to the evolutionarily conserved complex between PAR3, PAR6 and atypical PKC (aPKC) (Bradfield et al, 2007;Ebnet et al, 2004;Weber et al, 2007).…”

Section: Tricellulinmentioning

confidence: 99%

Tight junctions at a glance

Balda

Matter

2008

Journal of Cell Science

214

168

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“…It was first defined as an antigen for monoclonal antibodies that recognized TJs in epithelial cells, and it was subsequently revealed as a peripheral membrane protein with a molecular mass of 220 kDa, which underlied the cytoplasmic surface of plasma membranes of TJs (Stevenson et al, 1986). Evidence has accumulated that in epithelial cells, ZO-1 is exclusively located at TJs, but when TJs are not formed, it is concentrated in adherens junctions (AJs) (Itoh et al, 1993(Itoh et al, , 1999Furuse et al, 1994;Fanning et al, 1998;Bazzoni et al, 2000). In nonepithelial cells without TJs such as cardiac muscle cells and fibroblasts, ZO-1 is colocalized with cadherins to form AJs (Itoh et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

Deficiency of Zonula Occludens-1 Causes Embryonic Lethal Phenotype Associated with Defected Yolk Sac Angiogenesis and Apoptosis of Embryonic Cells

Katsuno

Umeda

Matsui

et al. 2008

MBoC

248

213

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Zonula occludens (ZO)-1/2/3 are the members of the TJ-MAGUK family of membrane-associated guanylate kinases associated with tight junctions. To investigate the role of ZO-1 (encoded by Tjp1) in vivo, ZO-1 knockout (Tjp1 ؊/؊ ) mice were generated by gene targeting. Although heterozygous mice showed normal development and fertility, delayed growth and development were evident from E8.5 onward in Tjp1 ؊/؊ embryos, and no viable Tjp1 ؊/؊ embryos were observed beyond E11.5. Tjp1 ؊/؊ embryos exhibited massive apoptosis in the notochord, neural tube area, and allantois at embryonic day (E)9.5. In the yolk sac, the ZO-1 deficiency induced defects in vascular development, with impaired formation of vascular trees, along with defective chorioallantoic fusion. Immunostaining of wild-type embryos at E8.5 for ZO-1/2/3 revealed that ZO-1/2 were expressed in almost all embryonic cells, showing tight junction-localizing patterns, with or without ZO-3, which was confined to the epithelial cells. ZO-1 deficiency depleted ZO-1-expression without influence on ZO-2/3 expression. In Tjp1 ؉/؉ yolk sac extraembryonic mesoderm, ZO-1 was dominant without ZO-2/3 expression. Thus, ZO-1 deficiency resulted in mesoderms with no ZO-1/2/3, associated with mislocalization of endothelial junctional adhesion molecules. As a result, angiogenesis was defected in Tjp1 ؊/؊ yolk sac, although differentiation of endothelial cells seemed to be normal. In conclusion, ZO-1 may be functionally important for cell remodeling and tissue organization in both the embryonic and extraembryonic regions, thus playing an essential role in embryonic development. INTRODUCTIONIn multicellular organisms, cell-cell adhesion is critical for development and morphogenesis. Various types of cell-cell adhesion-related molecules have been identified, and evidence has accumulated that their expression and functions are critically regulated in a spatiotemporally highly organized way (Tsukita et al., 2001;Halbleib and Nelson, 2006). In general, cell-cell adhesion molecules are integral membrane proteins that associate with peripheral membrane proteins to regulate and integrate cell-cell adhesion-related phenomena. Zonula occludens (ZO)-1 is a founding member of membrane-associated guanylate kinase (MAGUK) family proteins of tight junctions (TJs), composed of three postsynaptic density 95/disc-large/ZO-1 (PDZ) domains, a Src homology 3 domain, a guanylate kinase (GUK) domain, an acidic domain, and an actin binding region (Itoh et al., 1993; Willott et al., 1993;Jesaitis and Goodenough, 1996;Haskins et al., 1998). It was first defined as an antigen for monoclonal antibodies that recognized TJs in epithelial cells, and it was subsequently revealed as a peripheral membrane protein with a molecular mass of 220 kDa, which underlied the cytoplasmic surface of plasma membranes of TJs (Stevenson et al., 1986). Evidence has accumulated that in epithelial cells, ZO-1 is exclusively located at TJs, but when TJs are not formed, it is concentrated in adherens junctions (AJs) (Itoh et al., 199...

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Interaction of Junctional Adhesion Molecule with the Tight Junction Components ZO-1, Cingulin, and Occludin

Cited by 434 publications

References 53 publications

Junctional Adhesion Molecule A Interacts with Afadin and PDZ-GEF2 to Activate Rap1A, Regulate β1 Integrin Levels, and Enhance Cell Migration

Junctional Adhesion Molecule A Interacts with Afadin and PDZ-GEF2 to Activate Rap1A, Regulate β1 Integrin Levels, and Enhance Cell Migration

Tight junctions at a glance

Deficiency of Zonula Occludens-1 Causes Embryonic Lethal Phenotype Associated with Defected Yolk Sac Angiogenesis and Apoptosis of Embryonic Cells

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