Structure and Function of the Cell Surface (Tethered) Mucins

Hattrup, Christine L.; Gendler, Sandra J.

doi:10.1146/annurev.physiol.70.113006.100659

Cited by 661 publications

(680 citation statements)

References 143 publications

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“…Host cell attachment by IAV is mediated by the HA glycoprotein, which binds to specific types of Neu5Ac-containing receptors. 39 The towering structure of the MUC1 extracellular domain, estimated to be 200-500 nm in length when fully glycosylated, 21 plus expression of an abundance of terminally linked Neu5Ac is a likely first point of contact for HA binding by IAV that has penetrated the overlying gel mucus layer and gained access to the epithelial cell surface. Such chemoattraction and adherence to specific mucin carbohydrates have also been demonstrated for mouse adenovirus type I (MAVS-1) 40 and respiratory syncytial virus (RSV), 13 as well as bacteria including Campylobacter jejuni, 24 Helicobacter pylori 26 and Pseudomonas aeruginosa.…”

Section: Discussionmentioning

confidence: 99%

“…21 To establish whether MUC1, MUC13 and/or MUC16 can interact with IAV during the course of infection, we infected human type II alveolar epithelial (A549) cells with PR8 virus and at 1, 8, 16 and 24 h post infection (h.p.i. ), labeled the cells with antibody to PR8 virus and to cs-mucin and examined the colocalization of the labeling by confocal microscopy ( Figure 1ac and Supplementary Figure S1 online).…”

Section: The Cell Surface Mucin Muc1 Associates With Iavmentioning

confidence: 99%

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The cell surface mucin MUC1 limits the severity of influenza A virus infection

et al. 2017

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Cell surface mucin (cs-mucin) glycoproteins are constitutively expressed at the surface of respiratory epithelia where pathogens such as influenza A virus (IAV) gain entry into cells. Different members of the cs-mucin family each express a large and heavily glycosylated extracellular domain that towers above other receptors on the epithelial cell surface, a transmembrane domain that enables shedding of the extracellular domain, and a cytoplasmic tail capable of triggering signaling cascades. We hypothesized that IAV can interact with the terminal sialic acids presented on the extracellular domain of cs-mucins, resulting in modulation of infection efficiency. Utilizing human lung epithelial cells, we found that IAV associates with the cs-mucin MUC1 but not MUC13 or MUC16. Overexpression of MUC1 by epithelial cells or the addition of sialylated synthetic MUC1 constructs, reduced IAV infection in vitro. In addition, Muc1 À / À mice infected with IAV exhibited enhanced morbidity and mortality, as well as greater inflammatory mediator responses compared to wild type mice. This study implicates the cs-mucin MUC1 as a critical and dynamic component of the innate host response that limits the severity of influenza and provides the foundation for exploration of MUC1 in resolving inflammatory disease.

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Section: Discussionmentioning

confidence: 99%

Section: The Cell Surface Mucin Muc1 Associates With Iavmentioning

confidence: 99%

The cell surface mucin MUC1 limits the severity of influenza A virus infection

et al. 2017

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“…In normal epithelial cells, the physical interactions between the transmembrane mucin MUC1 and EGFR are prevented by their respective expression at the apical and basolateral side (Hattrup and Gendler, 2008). In contrast, in epithelial cancers MUC1 is often overexpressed and delocalized to the whole cell membrane and/or the cytoplasm thus allowing an interaction with EGFR.…”

Section: Discussionmentioning

confidence: 99%

“…MUC1 is a membrane-bound epithelial mucin (Hattrup and Gendler, 2008) composed of two subunits assembled by a non-covalent link, MUC1 N-terminal and MUC1 C-terminal (Ligtenberg et al, 1992). The MUC1 N-terminal subunit is a large extracellular 'mucin' subunit (4250 kDa) consisting of variable numbers of 20 amino-acid tandem repeats (TRs) on which are linked hundreds of O-glycans.…”

Section: Introductionmentioning

confidence: 99%

Galectin-3 regulates MUC1 and EGFR cellular distribution and EGFR downstream pathways in pancreatic cancer cells

et al. 2011

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MUC1 is a transmembrane glycoprotein which is typically expressed at the apical membrane of normal epithelial cells. In cancer cells, the over-expression of MUC1 and its aberrant localization around the cell membrane and in the cytoplasm favours its interaction with different protein partners such as epidermal growth factor receptor (EGFR) and can promote tumour proliferation through the activation of oncogenic signalling pathways. Our aims were to study the mechanisms inducing MUC1 cytoplasmic localization in pancreatic cancer cells, and to decipher their impact on EGFR cellular localization and activation. Our results showed that galectin-3, an endogenous lectin, is coexpressed with MUC1 in human pancreatic ductal adenocarcinoma, and that it favours the endocytosis of MUC1 and EGFR. Depletion of galectin-3 by RNA interference increased the interaction between MUC1 and EGFR, EGFR and ERK-1,2 phosphorylation, and translocation of EGFR to the nucleus. On the contrary, silencing of galectin-3 led to a decrease of cyclin-D1 levels and of cell proliferation. The galectin-3-dependent regulation of MUC1/EGFR functions may represent an interesting mechanism modulating the EGFR-stimulated cell growth of pancreatic cancer cells.

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“…The consequence of these altered glycosylation profiles results in the over accumulation of TACAs which are otherwise cryptic (masked) on healthy tissues. MUC1 is a membrane-bound mucin and is found in more than 90% of breast carcinomas (Hattrup, Gendler, 2008). Consequently, most efforts to provide classical carbohydrate-based vaccines have been devoted to the above antigens and the related ones ( Figure 3) (Ragupathi, 1996;Livingston, Ragupathi, 1997;Finn, 2003;Bast Jr et al, 2005).…”

Section: Glycodendrimer Vaccinesmentioning

confidence: 99%

Glycodendrimers: versatile tools for nanotechnology

Roy

Shiao

Rittenhouse-Olson

2013

Braz. J. Pharm. Sci.

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Combining nanotechnology with glycobiology has triggered an exponential growth of research activities in the design of novel functional bionanomaterials (glyconanotechnology). More specifically, recent synthetic advances towards the tailored and versatile design of glycosylated nanoparticles namely glyconanoparticles, considered as synthetic mimetics of natural glycoconjugates, paved the way toward diverse biomedical applications. The accessibility of a wide variety of these structured nanosystems, in terms of shapes, sizes, and organized around stable nanoparticles have readily contributed to their development and applications in nanomedicine. In this context, glycosylated gold-nanoparticles (GNPs), glycosylated quantum dots (QDs), fullerenes, single-wall natotubes (SWNTs), and self-assembled glycononanoparticles using amphiphilic glycopolymers or glycodendrimers have received considerable attention to afford powerful imaging, therapeutic, and biodiagnostic devices. This review will provide an overview of the most recent syntheses and applications of glycodendrimers in glycoscience that have permitted to deepen our understanding of multivalent carbohydrate-protein interactions. Together with synthetic breast cancer vaccines, inhibitors of bacterial adhesions to host tissues including sensitive detection devices, these novel bionanomaterials are finding extensive relevance.

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Structure and Function of the Cell Surface (Tethered) Mucins

Cited by 661 publications

References 143 publications

The cell surface mucin MUC1 limits the severity of influenza A virus infection

The cell surface mucin MUC1 limits the severity of influenza A virus infection

Galectin-3 regulates MUC1 and EGFR cellular distribution and EGFR downstream pathways in pancreatic cancer cells

Glycodendrimers: versatile tools for nanotechnology

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