Host α-adducin is redistributed and localized to the inclusion membrane in Chlamydia- and Chlamydophila-infected cells

Chu, Hencelyn; Weeks, Sara K.; Gilligan, Diana M.; Rockey, Daniel D.

doi:10.1099/mic.0.2008/020941-0

Cited by 8 publications

(6 citation statements)

References 31 publications

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“…143 Recent studies from our group also revealed that in epithelia a-adducin down-regulation results in loss of junctional assembly and reduced barrier integrity, 144 whereas in endothelial cells, severe disruption of VE-cadherinbased AJs was detected. 145 Similar to other studies where application of proapoptotic agents, cytokines or invading bacteria resulted in rapid removal of adducin from intercellular junctions, [146][147][148] we demonstrated a loss of adducin from endothelial junctions under treatment with inflammatory mediators such as lipopolysaccharide (LPS), TNF-a and thrombin. 145 However, how exactly adducin controls endothelial barrier integrity is not clear yet.…”

Section: Permeability Regulation By Abpssupporting

confidence: 85%

Mind the gap: mechanisms regulating the endothelial barrier

2017

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The endothelial barrier consists of intercellular contacts localized in the cleft between endothelial cells, which is covered by the glycocalyx in a sievelike manner. Both types of barrier-forming junctions, i.e. the adherens junction (AJ) serving mechanical anchorage and mechanotransduction and the tight junction (TJ) sealing the intercellular space to limit paracellular permeability, are tethered to the actin cytoskeleton. Under resting conditions, the endothelium thereby builds a selective layer controlling the exchange of fluid and solutes with the surrounding tissue. However, in the situation of an inflammatory response such as in anaphylaxis or sepsis intercellular contacts disintegrate in post-capillary venules leading to intercellular gap formation. The resulting oedema can cause shock and multi-organ failure. Therefore, maintenance as well as coordinated opening and closure of interendothelial junctions is tightly regulated. The two principle underlying mechanisms comprise spatiotemporal activity control of the small GTPases Rac1 and RhoA and the balance of the phosphorylation state of AJ proteins. In the resting state, junctional Rac1 and RhoA activity is enhanced by junctional components, actin-binding proteins, cAMP signalling and extracellular cues such as sphingosine-1-phosphate (S1P) and angiopoietin-1 (Ang-1). In addition, phosphorylation of AJ components is prevented by junction-associated phosphatases including vascular endothelial protein tyrosine phosphatase (VE-PTP). In contrast, inflammatory mediators inhibiting cAMP/Rac1 signalling cause strong activation of RhoA and induce AJ phosphorylation finally leading to endocytosis and cleavage of VE-cadherin. This results in dissolution of TJs the outcome of which is endothelial barrier breakdown.

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Section: Permeability Regulation By Abpssupporting

confidence: 85%

Mind the gap: mechanisms regulating the endothelial barrier

2017

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“…The membrane skeletal protein γ-adducin is localized at spectrin-actin junctions; it binds calmodulin and is an in vivo substrate for protein kinase C (PKC) and Rho-associated kinases. It regulates the remodeling of AJs in human epithelial cells and has been reported to be redistributed during bacterial infections ( 40 ). The downregulation of γ-adducin in our model of the bronchial epithelium gives intriguing insights into a potential role of this protein in the loss of stabilization of epithelial junctions during respiratory infections.…”

Section: Discussionmentioning

confidence: 99%

Dual RNA-seq of Nontypeable Haemophilus influenzae and Host Cell Transcriptomes Reveals Novel Insights into Host-Pathogen Cross Talk

Baddal¹,

Muzzi²,

Censini³

et al. 2015

mBio

103

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The ability to adhere and adapt to the human respiratory tract mucosa plays a pivotal role in the pathogenic lifestyle of nontypeable Haemophilus influenzae (NTHi). However, the temporal events associated with a successful colonization have not been fully characterized. In this study, by reconstituting the ciliated human bronchial epithelium in vitro, we monitored the global transcriptional changes in NTHi and infected mucosal epithelium simultaneously for up to 72 h by dual RNA sequencing. The initial stage of colonization was characterized by the binding of NTHi to ciliated cells. Temporal profiling of host mRNA signatures revealed significant dysregulation of the target cell cytoskeleton elicited by bacterial infection, with a profound effect on the intermediate filament network and junctional complexes. In response to environmental stimuli of the host epithelium, NTHi downregulated its central metabolism and increased the expression of transporters, indicating a change in the metabolic regime due to the availability of host substrates. Concurrently, the oxidative environment generated by infected cells instigated bacterial expression of stress-induced defense mechanisms, including the transport of exogenous glutathione and activation of the toxin-antitoxin system. The results of this analysis were validated by those of confocal microscopy, Western blotting, Bio-plex, and real-time quantitative reverse transcription-PCR (qRT-PCR). Notably, as part of our screening for novel signatures of infection, we identified a global profile of noncoding transcripts that are candidate small RNAs (sRNAs) regulated during human host infection in Haemophilus species. Our data, by providing a robust and comprehensive representation of the cross talk between the host and invading pathogen, provides important insights into NTHi pathogenesis and the development of efficacious preventive strategies.

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“…This novel function of adducins could be important for remodeling of epithelial junctions during embryonic morphogenesis, a steady-state rejuvenation of epithelial layers, and restoration of epithelial barrier during wound healing. Furthermore, given the fact that adducins can be rapidly removed from intercellular junctions and degraded by cytokines (Pariser et al , 2005), invading bacteria (Chu et al , 2008), and proapoptotic agents (van de Water et al , 2000), adducins dysfunctions could mediate disruption of epithelial barriers during infection and inflammation. Further studies are required to test the roles of these membrane skeleton proteins in mucosal diseases.…”

Section: Discussionmentioning

confidence: 99%