Cholesterol depletion alters detergent-specific solubility profiles of selected tight junction proteins and the phosphorylation of occludin

Lynch, Robert D.; Francis, Stacy A.; McCarthy, Karin M.; Casas, Elizabeth; Thiele, Christoph; Schneeberger, Eveline E.

doi:10.1016/j.yexcr.2007.05.009

Cited by 38 publications

(44 citation statements)

References 42 publications

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“…However, although endocytosis is demonstrably an important component of the response to cytokines (Foerg et al, 2007), another role for caveolin is the organization of lipid-dependent signaling domains (Wei et al, 1999).We speculate that extra occludin in MDCK cells could be acting to enhance association with, and therefore the response to, these signaling molecules; occludin KD could have the opposite effect. This hypothesis is supported not only by the occludin-dependent change in caveolin localization demonstrated in this study, but also by published studies demonstrating that occludin can immunoprecipitate caveolin (Nusrat et al, 2000;Lynch et al, 2007). Furthermore, caveolin but not occludin binds cholesterol, yet the disruption to the function of tight junction barriers caused by removal of cholesterol is dependent on the presence of occludin (Yu et al, 2005).…”

Section: Discussionsupporting

confidence: 84%

“…In addition, previous studies demonstrated that caveolin-1 is widely distributed throughout the cell on the apical and basolateral cell membranes and in intracellular vesicles but that a fraction colocalizes and is physically associated with occludin. For example, occludin coimmunoprecipitates with caveolin (Nusrat et al, 2000;Lynch et al, 2007), the two proteins colocalize at the tight junction at the ultrastructural level as revealed by immuno-gold techniques (Nusrat et al, 2000), and when endocytosis is stimulated they can be found in the same vesicles (Shen and Turner, 2005; Stamatovic et al, 2009). These observations led us to investigate whether depleting occludin might alter the distribution of caveolin-1.…”

Section: Depletion Of Occludin Alters Localization Of Caveolin-1mentioning

confidence: 99%

“…Along with a putative role in trafficking, a second characteristic shared by many Marvel domain family members is an association with lipid rafts, cholesterol and/or caveolin. Occludin itself was shown to be a component of a detergent-resistant membrane microdomain (Nusrat et al, 2000;Lambert et al, 2005;Lynch et al, 2007) and several studies have implicated the importance of a cholesterol-rich membrane domain in tight junction function. For example, removal of cholesterol from wild-type MDCK cells results in decreased transepithelial electrical resistance (TER), but has no effect on TER in occludindepleted MDCK cells (Yu et al, 2005).…”

Section: Introductionmentioning

confidence: 99%

“…For example, removal of cholesterol from wild-type MDCK cells results in decreased transepithelial electrical resistance (TER), but has no effect on TER in occludindepleted MDCK cells (Yu et al, 2005). In addition, occludin has also been demonstrated in co-immunoprecipitation experiments to interact with the cholesterol-binding protein caveolin-1 (Nusrat et al, 2000;Lynch et al, 2007). There is significant evidence that occludin functions within a lipid microdomain, although it remains unclear whether occludin plays an active or passive role in organizing this microdomain.…”

Section: Introductionmentioning

confidence: 99%

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Occludin is required for cytokine-induced regulation of tight junction barriers

Itallie

Fanning

Holmes

et al. 2010

Journal of Cell Science

173

168

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SummaryThe function of occludin remains elusive. Proposed roles include maintenance of tight junction barriers, signaling and junction remodeling. To investigate a potential role in mediating cytokine-induced changes in barrier properties, we measured barrier responses to interferon- plus TNF in control, occludin-overexpressing and occludin knockdown MDCK II monolayers. MDCK cells show a complex response to cytokines characterized by a simultaneous increase in the transepithelial electrical resistance and a decrease in the barrier for large solutes. We observed that overexpression of occludin increased and occludin knockdown decreased sensitivity to cytokines as assessed by both these parameters. It is known that caveolin-1 interacts with occludin and is implicated in several models of cytokine-dependent barrier disruption; we found that occludin knockdown altered the subcellular distribution of caveolin-1 and that partitioning of caveolin into detergent-insoluble lipid rafts was influenced by changing occludin levels. Knockdown of caveolin decreased the cytokine-induced flux increase, whereas the increase in the electrical barrier was unaltered; the effect of double knockdown of occludin and caveolin was similar to that of occludin single knockdown, consistent with the possibility that they function in the same pathway. These results demonstrate that occludin is required for cells to transduce cytokine-mediated signals that either increase the electrical barrier or decrease the large solute barrier, possibly by coordinating the functions of caveolin-1.

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Section: Discussionsupporting

confidence: 84%

Section: Depletion Of Occludin Alters Localization Of Caveolin-1mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Occludin is required for cytokine-induced regulation of tight junction barriers

Itallie

Fanning

Holmes

et al. 2010

Journal of Cell Science

173

168

View full text Add to dashboard Cite

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“…Regardless of the model, lipids are important for tight junctions. For example, some tight junction proteins are associated with cholesterol-rich, detergent-resistant membrane microdomains and modification of cholesterol modifies epithelial barrier properties [67][68][69] . However, freeze-fracture analysis of tight junctions of cholesterol depleted cells yielded contradictory results, and cholesterol may affect a membrane by influencing the lipid structure or the functional properties of transmembrane proteins by altering their lipid environment 70,71 .…”

Section: Models Of Tight Junction Structurementioning

confidence: 99%

Tight junctions: from simple barriers to multifunctional molecular gates

Zihni

Mills

Matter

et al. 2016

Nat Rev Mol Cell Biol

998

804

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Main body of text: 5983 words 2Epithelia and endothelia separate different tissue compartments and protect multicellular organisms form the outside world. This requires the formation of tight junctions, selective gates that control paracellular diffusion of ions and solutes. Tight junctions also form the border between the apical and basolateral plasma membrane domains and are linked to the machinery that controls apicobasal polarization. Additionally, signalling networks that guide diverse cell behaviours and functions are connected to tight junctions, transmitting information to and from the cytoskeleton, nucleus and different cell adhesion complexes. Here, we discuss recent advances in our understanding of the molecular architecture and cellular functions of tight junctions.Microscopists in the 19 th century described the paracellular space between neighbouring cells within an epithelial sheet to be sealed by a "terminal bar", a structure later resolved by electron microscopy into a composite of distinct cell-cell junctions that is now called the epithelial junctional complex and is formed by tight junctions, adherens junctions and desmosomes 1,2 . As the former two junctions are more tightly associated and often reside at the apical end of the lateral membrane, they are often referred to as the apical junctional complex (however, in endothelia, tight junctions and adherens junctions can be intercalated) (Fig. 1). Tight junctions are essential for barrier formation, and their primary physiological role is to function as paracellular gates that restrict diffusion on the basis of size and charge. Selective paracellular diffusion is an essential process for the maintenance of homoeostasis in organs and tissues. Tight junctions have long been the most enigmatic of all adhesion complexes and eluded a detailed molecular and functional analysis due to their complex architecture. Recent years have witnessed the identification of a large array of components associated with tight junctions implicating these junctions in an unexpected range of different functions, thereby challenging the traditional model, in which tight junctions are considered a simple diffusion barrier formed by a rigid molecular complex. In line with these various functions, mutations in genes encoding tight junction proteins have been linked to a range of inherited human diseases. Additionally, tight junction components are known to be targeted by a number of pathogenic bacteria and viruses, which hijack tight junction proteins to enter and infect cells, or target junctional signalling mechanisms to cross tissue barriers. Although tight junctions are a vertebrate junction, many of their components and functions are evolutionarily conserved (Box 1).The main purpose of this review is to examine the recent advances in the unravelling of the molecular architecture of tight junctions and understanding their functions. We will discuss recent exciting insights into how tight junctions function as signalling platforms that guide cell behaviour and differen...

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