Mucin Granules are in Close Contact with Tubular Elements of the Endoplasmic Reticulum

Pérez-Vilar, Juan; Ribeiro, Carla M. P.; Salmon, W. D.; Mabolo, Raean; Boucher, Richard C.

doi:10.1369/jhc.5b6713.2005

Cited by 10 publications

(6 citation statements)

References 10 publications

(18 reference statements)

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“…Notably, the ER network is not restricted to a perinuclear localization and extends towards the apical pole of airway epithelia, where ER tubules have been described to be in close apposition with the mucin granules in goblet cells from HBE. 28 As IRE1β is an ER-resident protein, it is not surprising to see its staining throughout the goblet cell theca where post-Golgi mucin granules are stored (Figure 2a). Quantification of the IRE1β immunostain confirmed that its expression is upregulated in CF as compared with normal HBE (Figure 2b).…”

Section: Resultsmentioning

confidence: 99%

The ER stress transducer IRE1β is required for airway epithelial mucin production

et al. 2013

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Inflammation of human bronchial epithelia (HBE) activates the endoplasmic reticulum (ER) stress transducer inositolrequiring enzyme 1 (IRE1)α, resulting in IRE1α-mediated cytokine production. Previous studies demonstrated ubiquitous expression of IRE1α and gut-restricted expression of IRE1β.We found that IRE1β is also expressed in HBE, is absent in human alveolar cells, and is upregulated in cystic fibrosis and asthmatic HBE. Studies with Ire1β−/− mice and Calu-3 airway epithelia exhibiting IRE1β knockdown or overexpression revealed that IRE1β is expressed in airway mucous cells, is functionally required for airway mucin production, and this function is specific for IRE1β vs. IRE1α. IRE1β-dependent mucin production is mediated, at least in part, by activation of the transcription factor X-box binding protein-1 (XBP-1) and the resulting XBP-1-dependent transcription of anterior gradient homolog 2, a gene implicated in airway and intestinal epithelial mucin production. These novel findings suggest that IRE1β is a potential mucous cell-specific therapeutic target for airway diseases characterized by mucin overproduction.

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Section: Resultsmentioning

confidence: 99%

The ER stress transducer IRE1β is required for airway epithelial mucin production

et al. 2013

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“…Adhesion of epithelial cells to their neighbors and extracellular matrix is governed by adhesion complexes, and the integrin-interacting CALR is associated with the adhesion complex of the focal junctions ( 53 ). Thin calreticulin-containing tubules that encircle mucin granules of goblet cells are in close contact with endoplasmic reticulum tubules ( 54 ). The increased presence of the goblet cells and the significant upregulation of Calr in the probiotic group point to the key role of this protein in many of the cellular and immunoregulatory functions, which help to counter the inflammation.…”

Section: Discussionmentioning

confidence: 99%

A Microbial Feed Additive Abates Intestinal Inflammation in Atlantic Salmon

et al. 2015

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The efficacy of a microbial feed additive (Bactocell®) in countering intestinal inflammation in Atlantic salmon was examined in this study. Fish were fed either the additive-coated feed (probiotic) or feed without it (control). After an initial 3-week feeding, an inflammatory condition was induced by anally intubating all the fish with oxazolone. The fish were offered the feeds for 3 more weeks. Distal intestine from the groups was obtained at 4 h, 24 h, and 3 weeks, after oxazolone treatment. Inflammatory responses were prominent in both groups at 24 h, documented by changes in intestinal micromorphology, expression of inflammation-related genes, and intestinal proteome. The control group was characterized by edema, widening of intestinal villi and lamina propria, infiltration of granulocytes and lymphocytes, and higher expression of genes related to inflammatory responses, mul1b, il1b, tnfa, ifng, compared to the probiotic group or other time points of the control group. Further, the protein expression in the probiotic group at 24 h after inducing inflammation revealed five differentially regulated proteins – Calr, Psma5, Trp1, Ctsb, and Naga. At 3 weeks after intubation, the inflammatory responses subsided in the probiotic group. The findings provide evidence that the microbial additive contributes to intestinal homeostasis in Atlantic salmon.

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“…Moreover, an ion exchange (Ca 2ϩ /K ϩ )-triggered phase transition of the matrix is thought to occur prior to and/or during granule exocytosis, resulting in matrix decondensation and hydration and discharge of entrapped secretory proteins (24,25). Recent studies in live mucous/goblet cells have revealed novel aspects on mucous/goblet cells and their granules (26,27). Thus, fluorescence recovery after photobleaching (FRAP) 2 analyses with a mucin-GFP fusion protein suggested that the mucin granule lumen is compartmentalized into a mobile or fluid phase, in which secretory products diffused very slowly, and an immobile, pH-dependent phase (i.e.…”

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confidence: 99%