The cell polarity protein ASIP/PAR-3 directly associates with junctional adhesion molecule (JAM)

Ebnet, Klaus; Suzuki, Atsushi; Horikoshi, Yosuke; Hirose, Tomonori; Brickwedde, Maria Katharina Meyer Zu; Ohno, Shigeo; Vestweber, Dietmar

doi:10.1093/emboj/20.14.3738

Cited by 355 publications

(321 citation statements)

References 44 publications

(90 reference statements)

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“…Could the JAM-A-induced contacts seen in our study represent a selection site? The location of the contacts between adjacent cells is consistent with this hypothesis, as is the presence of endogenous occludin, ZO-1, and PAR3 proteins found with JAM in other cell types (16,17,47). However, others have proposed that E-cadherin may function as a targeting patch for development of the hepatic phenotype (12).…”

Section: What Does Simple 3 Hepatic Maturation Require?supporting

confidence: 74%

“…First, ZO-1 is an early player for junction formation in epithelia (73), and JAM-A is not far behind (20). Second, PAR3 is a member of the PAR/ aPKC complex (17,26), which is required for establishing and maintaining TJs in epithelia, and JAM is the only known membrane anchor for it (reviewed in Refs. 49,62).…”

Section: Jam-a's Cytoplasmic Pdz-binding Domain Is Essential For Its mentioning

confidence: 99%

“…Nonetheless, results from the in vitro studies suggest that JAM plays an essential and early role in TJ formation (17,26,38), since it was found at primordial cell-cell contact sites in a bronchial epithelial cell line (31).…”

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confidence: 99%

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JAM-A is both essential and inhibitory to development of hepatic polarity in WIF-B cells

Braiterman¹,

Heffernan²,

Nyasae³

et al. 2008

American Journal of Physiology-Gastrointestinal and Liver Physi

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Junctional adhesion molecule (JAM) is involved in tight junction (TJ) formation in epithelial cells. Three JAMs (A, B, and C) are expressed in rat hepatocytes, but only rat JAM-A is present in polarized WIF-B cells, a rat-human hepatic line. We used knockdown (KD) and overexpression in WIF-B cells to determine the role of JAM-A in the development of hepatic polarity. Expression of rat JAM-A short hairpin RNA resulted in ϳ50% KD of JAM-A and substantial loss of hepatic polarity, as measured by the absence of apical cysts formed by adjacent cells and sealed by TJ belts. When inhibitory RNA-resistant human JAM-A (huWT) was expressed in KD cells, hepatic polarity was restored. In contrast, expression of JAM-A that either lacked its PDZ-binding motif (hu⌬C-term) or harbored a point mutation (T273A) did not complement, indicating that multiple sites within JAM-A's cytoplasmic tail are required for the development of hepatic polarity. Overexpression of huWT in normal WIF-B cells unexpectedly blocked WIF-B maturation to the hepatic phenotype, as did expression of three huJAM-A constructs with single point mutations in putative phosphorylation sites. In contrast, hu⌬C-term was without effect, and the T273A mutant only partially blocked maturation. Our results show that JAM-A is essential for the development of polarity in cultured hepatic cells via its possible phosphorylation and recruitment of relevant PDZ proteins and that hepatic polarity is achieved within a narrow range of JAM-A expression levels. Importantly, formation/ maintenance of TJs and the apical domain in hepatic cells are linked, unlike simple epithelia.partitioning-defective polarity protein/atypical protein kinase C complex

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Section: What Does Simple 3 Hepatic Maturation Require?supporting

confidence: 74%

Section: Jam-a's Cytoplasmic Pdz-binding Domain Is Essential For Its mentioning

confidence: 99%

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JAM-A is both essential and inhibitory to development of hepatic polarity in WIF-B cells

Braiterman¹,

Heffernan²,

Nyasae³

et al. 2008

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…48 bEnd.5 endothelioma cells were grown on LabTek chamber slides (NalgeneNunc, Wiesbaden, Germany) and stained as described previously. 49 Phase contrast microscopy was performed on a Leica DM RXA microscope (Leica Microsystems, Wetzlar Germany). Abs are described in Supplementary material.…”

Section: Discussionmentioning

confidence: 99%

Granzyme B is expressed in mouse mast cells in vivo and in vitro and causes delayed cell death independent of perforin

Pardo

Wallich

Ebnet³

et al. 2007

Cell Death Differ

122

130

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Mast cells respond to pathogens and allergens by secreting a vast array of preformed and newly synthesized mediators, including enzymes, vasoactive amines, lipid mediators, cytokines and chemokines, thereby affecting innate and adaptive immune responses and pathogenesis. Here, we present evidence that skin-, but not lung-associated primary mast cells as well as in vitro-differentiated bone marrow-derived mast cells (BMMC) express granzyme (gzm) B, but not gzmA or perforin (perf). GzmB is associated with cytoplasmic granules of BMMC and secreted after Fce-receptor-mediated activation. BMMC from wild type but not gzmB-deficient mice cause cell death in susceptible adherent target cells, indicating that the perf-independent cytotoxicity of BMMC is executed by gzmB. Furthermore, gzmB induces a disorganization of endothelial cell-cell contacts. The data suggest that activated mast cells contribute, via secreted gzmB, to cell death, increased vascular permeability, leukocyte extravasation and subsequent inflammatory processes in affected tissues.

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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

159

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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The cell polarity protein ASIP/PAR-3 directly associates with junctional adhesion molecule (JAM)

Cited by 355 publications

References 44 publications

JAM-A is both essential and inhibitory to development of hepatic polarity in WIF-B cells

JAM-A is both essential and inhibitory to development of hepatic polarity in WIF-B cells

Granzyme B is expressed in mouse mast cells in vivo and in vitro and causes delayed cell death independent of perforin

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

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