Membrane asymmetry in epithelia: is the tight junction a barrier to diffusion in the plasma membrane?

Dragsten, Paul R.; Blumenthal, Robert; Handler, Jerome S.

doi:10.1038/294718a0

Cited by 341 publications

(171 citation statements)

References 31 publications

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“…Canalicular Fic1 may indirectly control lipid distribution in the inner basolateral membrane leaflet as a result of tangential lipid flow between the canalicular and basolateral compartments bypassing the tight junction, which imposes a barrier only in the outer leaflet. 31 Both indirect and direct evidence support the conclusion that Fic1 is an ATP-dependent aminophospholipid translocase. The indirect evidence is substantially greater ATP-dependent aminophospholipid translocase activity in the canalicular membrane when compared with activity in the basolateral membrane.…”

Section: Discussionsupporting

confidence: 50%

Familial intrahepatic cholestasis 1: Studies of localization and function

et al. 2001

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Section: Discussionsupporting

confidence: 50%

Familial intrahepatic cholestasis 1: Studies of localization and function

et al. 2001

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“…Tight junctions are essential for BBB properties not only by restricting the passive diffusion of ions or macromolecules, 2 but also by preventing the lateral diffusion of lipids and integral membrane proteins, thus controlling the brain endothelial apicobasal polarity. 3 Tight junction complexes are composed of transmembrane proteins, notably claudin (cldn) À 3, À 5 2 and occludin, 4 which are crucial to maintain TJ integrity together with several immunoglobulin superfamily members, such as junctional adhesion molecules. 5 In addition, cytosolic proteins, such as the ZO family (ZO À 1, À 2, À 3) directly bind the intracellular domains of these transmembrane proteins and act as molecular links to the cytoskeleton and signal transducers.…”

Section: Introductionmentioning

confidence: 99%

The Wnt/Planar Cell Polarity Signaling Pathway Contributes to the Integrity of Tight Junctions in Brain Endothelial Cells

Artus

Glacial

Ganeshamoorthy

et al. 2013

J Cereb Blood Flow Metab

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Wnt morphogens released by neural precursor cells were recently reported to control blood-brain barrier (BBB) formation during development. Indeed, in mouse brain endothelial cells, activation of the Wnt/b-catenin signaling pathway, also known as the canonical Wnt pathway, was shown to stabilize endothelial tight junctions (TJs) through transcriptional regulation of the expression of TJ proteins. Because Wnt proteins activate several distinct b-catenin-dependent and independent signaling pathways, this study was designed to assess whether the noncanonical Wnt/Par/aPKC planar cell polarity (PCP) pathway might also control TJ integrity in brain endothelial cells. First we established, in the hCMEC/D3 human brain endothelial cell line, that the Par/aPKC PCP complex colocalizes with TJs and controls apicobasal polarization. Second, using an siRNA approach, we showed that the Par/aPKC PCP complex regulates TJ stability and reassembling after osmotic shock. Finally, we provided evidence that Wnt5a signals in hCMEC/D3 cells through activation of the Par/aPKC PCP complex, independently of the Wnt canonical b-catenin-dependent pathway and significantly contributes to TJ integrity and endothelial apicobasal polarity. In conclusion, this study suggests that the Wnt/Par/aPKC PCP pathway, in addition to the Wnt/b-catenin canonical pathway, is a key regulator of the BBB.

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“…[10][11][12][13][14][15] Tight junctions, situated at the membrane between apical and lateral regions of polarised epithelial cells, selectively regulate the passage of molecules and ions via the paracellular pathway, 16 and also restrict the lateral movement of molecules in the cell membrane. 17,18 Proteins of the tight junction include integral membrane proteins claudins and occludin, cytoplasmic cytoskeletal linker proteins, ZO-1, ZO-2 and ZO-3, and also many signalling molecules such as aPKC, Rho proteins, PKC-z, c-Yes and PI3-kinase. 11,14 In addition, other proteins are associated with tight junctions that may have proliferative and differentiative capacity such as transcription factors, lipid phosphatases and cell cycle regulators.…”

mentioning

confidence: 99%

Inflammatory processes have differential effects on claudins 2, 3 and 4 in colonic epithelial cells

Prasad

Mingrino

Kaukinen

et al. 2005

Laboratory Investigation

430

384

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Claudin proteins comprise a recently described family of tight junction proteins that differentially regulate paracellular permeability. Since other tight junction proteins show alterations in distribution or expression in inflammatory bowel disease (IBD) we assessed expression of claudins (CL) 2, 3 and 4 in IBD. CL 2 was strongly expressed along the inflamed crypt epithelium, whilst absent or barely detectable in normal colon. In contrast, CL 3 and 4 were present throughout normal colonic epithelium and were reduced or redistributed in the diseased surface epithelium. In a T84-cell culture model of the gut barrier, paracellular permeability decreased with time after plating and correlated with a marked decrease in the expression of CL 2. Addition of IFNc/TNFa led to further decreases in CL 2 and 3, the redistrbution of CL 4 and a marked increase in paracellular permeability. Conversely, IL-13 dramatically increased CL 2, with little effect on CL 3 or 4, but also resulted in increased paracellular permeability. Expression of CL 2 did not correlate with proliferation or junctional reorganisation after calcium ion depletion. Re-expression of CL 2 in response to IL-13 was inhibited by phophatidylinositol 3 kinase inhibitor, LY294002, which also restored the ion permeability to previous levels. CL 2 expression could be stimulated in the absence of IL-13 by activation of phospho-Akt in the phophatidylinositol 3 kinase pathway. These results suggest that INFc/TNFa and IL-13 have differential effects on CL 2, 3 and 4 in tight junctions, which may lead to increased permeability via different mechanisms.

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Membrane asymmetry in epithelia: is the tight junction a barrier to diffusion in the plasma membrane?

Cited by 341 publications

References 31 publications

Familial intrahepatic cholestasis 1: Studies of localization and function

Familial intrahepatic cholestasis 1: Studies of localization and function

The Wnt/Planar Cell Polarity Signaling Pathway Contributes to the Integrity of Tight Junctions in Brain Endothelial Cells

Inflammatory processes have differential effects on claudins 2, 3 and 4 in colonic epithelial cells

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