aPKC phosphorylates JAM-A at Ser285 to promote cell contact maturation and tight junction formation

Iden, Sandra; Misselwitz, Steve; Peddibhotla, Swetha S. D.; Tuncay, Hüseyin; Rehder, Daniela; Gerke, Volker; Robenek, Horst; Suzuki, Atsushi; Ebnet, Klaus

doi:10.1083/jcb.201104143

Cited by 90 publications

(95 citation statements)

References 60 publications

(103 reference statements)

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“…A large body of evidence shows that interference in the interactions between TJ proteins perturbs the TJs affecting the barrier permeability of the endothelium ( 38 ). It was further observed that the TJ formation or disintegration depends on the phosphorylation state of TJ proteins (39)(40)(41). However, most of these studies were focused on epithelial TJs, and therefore, the role of phosphorylation of TJ proteins in the preservation or perturbation of endothelial TJ integrity and its barrier function has not been well-studied.…”

Section: Xo-dependent Ros Production Mediates 15(s)-heteinduced Jama mentioning

confidence: 99%

12/15-Lipoxygenase-dependent ROS production is required for diet-induced endothelial barrier dysfunction

Chattopadhyay

Tinnikov

Dyukova

et al. 2015

Journal of Lipid Research

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This article is available online at http://www.jlr.org surface to the circulating blood, and releases vasoactive substances involved in the regulation of vascular tone ( 1, 2 ). Besides, it selectively permits the movement of molecules into and out of the bloodstream, and this semipermeable capacity of the endothelial monolayer depends majorly on cell-to-cell connections, namely adherens junctions (AJs), tight junctions (TJs), and gap junctions ( 3, 4 ). Disruption of these junctions leads to a leaky endothelial barrier, which allows the traffi cking of leukocytes through the blood vessels into the interstitial space and initiates infl ammation ( 2, 4 ). A large body of evidence indicates that TJs of endothelium play a pivotal role in modulating its barrier permeability, and dysfunctional endothelium often manifests increased barrier permeability ( 5, 6 ). Many studies suggest that oxidative stress is one of the underlying factors in endothelial dysfunction and atherosclerosis ( 7,8 ). NADPH oxidase, a major source of reactive oxygen species (ROS) production ( 9 ), has been reported to increase EC barrier permeability ( 10, 11 ). Xanthine oxidase (XO), a purine-catabolizing enzyme, was also found as another major source of cellular ROS production ( 12 ). XO results from sulfhydryl oxidation or proteolytic conversion of xanthine dehydrogenase (XDH) ( 13,14 ). Although both XDH and XO convert hypoxanthine and xanthine to uric acid, XO preferentially converts molecular oxygen to superoxide anion and hydrogen peroxide ( 12 ). However, under the reduced state, XDH can also react with molecular oxygen and generate ROS ( 15 ). Although the physiological signifi cance of XDH conversion to XO is not clear, XO was found to be abundantly present in several tissues, including in the luminal surface of the microvascular endothelium, and is thought to be involved in the pathogenesis of various diseases such as infl ammation and Endothelium, which is constituted by a monolayer of endothelial cells (ECs), is the inner most lining of the blood vessels, provides nonplatelet adherent nonthrombotic Abstract To understand the mechanisms of 15(S)-HETEinduced endothelial cell (EC) barrier dysfunction, we examined the role of xanthine oxidase (XO). 15(S)-HETE induced

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Section: Xo-dependent Ros Production Mediates 15(s)-heteinduced Jama mentioning

confidence: 99%

12/15-Lipoxygenase-dependent ROS production is required for diet-induced endothelial barrier dysfunction

Chattopadhyay

Tinnikov

Dyukova

et al. 2015

Journal of Lipid Research

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“…JAM-A was detected in nonpermeabilized cells, with most of the signal showing a typical honeycomb pattern (Fig. 1A), similar to that observed in polarized cells (Iden et al, 2012). Occludin and ZO-1 were also readily detected at the intercellular junctions when the cells were permeabilized, although a large proportion of ZO-1 appeared dispersed in the cytoplasm ( Fig.…”

Section: Resultsmentioning

confidence: 63%

The tight junction protein JAM-A functions as coreceptor for rotavirus entry into MA104 cells

et al. 2015

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Several molecules have been identified as receptors or coreceptors for rotavirus infection, including glycans, integrins, and hsc70. In this work we report that the tight junction proteins JAM-A, occludin, and ZO-1 play an important role during rotavirus entry into MA104 cells. JAM-A was found to function as coreceptor for rotavirus strains RRV, Wa, and UK, but not for rotavirus YM. Reassortant viruses derived from rotaviruses RRV and YM showed that the virus spike protein VP4 determines the use of JAM-A as coreceptor.

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“…Disruption in the interactions between these proteins perturbs the TJs affecting the permeability of the endothelium (22). Although the steady-state levels of transmembrane and intracellular TJ components are critical in the formation of TJ complexes, many studies have also reported that post-translational modifications, such as phosphorylation, play a role in the regulation of TJs (35,38,40,42,43). In this aspect, a role for both Ser/Thr and Tyr phosphorylation of TJ proteins in the formation and/or disruption of TJs has been reported (40, 44 -46).…”

Section: Discussionmentioning

confidence: 99%

Vascular Endothelial Tight Junctions and Barrier Function Are Disrupted by 15(S)-Hydroxyeicosatetraenoic Acid Partly via Protein Kinase Cϵ-mediated Zona Occludens-1 Phosphorylation at Threonine 770/772

Chattopadhyay

Dyukova

Singh

et al. 2014

Journal of Biological Chemistry

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Background: Tight junctions play an essential role in the maintenance of endothelial barrier function. Results: 15(S)-HETE stimulated ZO-1 phosphorylation at Thr-770/772 residues in PKC⑀-dependent MEK1-ERK1/2 activation disrupting endothelial tight junctions and barrier function. Conclusion: PKC⑀ by interrupting ZO-1 and occludin interactions plays a role in 15(S)-HETE-induced endothelial TJ disruption. Significance: 12/15-Lipoxygenase appears to be a crucial player in the modulation of endothelial barrier permeability.

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aPKC phosphorylates JAM-A at Ser285 to promote cell contact maturation and tight junction formation

Abstract: The PAR-3–aPKC–PAR-6 complex is recruited to primordial cell–cell junctions, in which aPKC phosphorylates JAM-A to promote junctional maturation.

Cited by 90 publications

References 60 publications

12/15-Lipoxygenase-dependent ROS production is required for diet-induced endothelial barrier dysfunction

12/15-Lipoxygenase-dependent ROS production is required for diet-induced endothelial barrier dysfunction

The tight junction protein JAM-A functions as coreceptor for rotavirus entry into MA104 cells

Vascular Endothelial Tight Junctions and Barrier Function Are Disrupted by 15(S)-Hydroxyeicosatetraenoic Acid Partly via Protein Kinase Cϵ-mediated Zona Occludens-1 Phosphorylation at Threonine 770/772

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