Comparison of the Transmembrane Mucins MUC1 and MUC16 in Epithelial Barrier Function

Gipson, Ilene K.; Spurr-Michaud, Sandra; Tisdale, Ann; Menon, Balaraj B.

doi:10.1371/journal.pone.0100393

Cited by 105 publications

(108 citation statements)

References 47 publications

(101 reference statements)

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“…In experiments in which MUC16 was stably knocked down, the functions of MUC16 on the apical surface of human corneal epithelial cells in culture was recently tested (Blalock et al, 2007; Gipson et al, 2014). The data demonstrated that MUC16 provided barrier function at the epithelial surface.…”

Section: Discussionmentioning

confidence: 99%

Human conjunctival goblet cells express the membrane associated mucin MUC16: Localization to mucin granules

Gipson

Spurr-Michaud

Tisdale

2016

Experimental Eye Research

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MUC16 is an extraordinarily large 22,152 amino acid membrane spanning mucin that has been shown to be present in the glycocalyx of the apical cells of the human cornea and conjunctiva where is interfaces with the tear film. The ectodomain of the molecule has been demonstrated in tears, where it has been presumed to be from surface epithelial cells. Data presented here from multiple assays, including immunohistochemistry, immunoelectron microscopy, in situ hybridization, and RT-PCR of RNA isolated from goblet cells isolated by laser capture microdissection, demonstrate that the membrane tethered mucin is also expressed by conjunctival goblet cells both in humans and in mice. The mucin is present in mucin granules and appears to be localized to the mucin granule membrane. Correlation analyses of the amounts of the goblet cell secreted mucin MUC5AC and the amounts of MUC16 and of MUC1 another membrane tethered mucin ectodomain found in human tear samples demonstrated that MUC5AC amounts correlated to the amounts of MUC16 but not to MUC1. These data suggest that goblet cells are a second source of the mucin in tears. The function of the membrane tethered mucin in the mucin granule remains to be determined.

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Section: Discussionmentioning

confidence: 99%

Human conjunctival goblet cells express the membrane associated mucin MUC16: Localization to mucin granules

Gipson

Spurr-Michaud

Tisdale

2016

Experimental Eye Research

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“…MUC1 in gastric epithelial cells acted as a releasable decoy receptor against Helicobacter pylori that limited bacterial infection (32) and attenuated H. pylori-driven proinflammatory cytokine release (33,34). In other studies, whereas both MUC1 and MUC16 were expressed in corneal epithelial cells, only MUC16 provided a barrier to bacterial adherence (35). Our unpublished results revealed that MUC1 gene expression in M1-polarized hMDMs was highest among the membrane-bound mucins examined (MUC4, MUC16, MUC18, MUC20, MUC21, and MUC22).…”

Section: Muc1/muc1 Deficiency Enhances Ros Production and Tnf-a Releamentioning

confidence: 90%

Membrane-Tethered MUC1 Mucin Counter-Regulates the Phagocytic Activity of Macrophages

Kato

Uchino

Lillehoj

et al. 2016

Am J Respir Cell Mol Biol

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MUC1 (MUC in human; Muc in animals) is a transmembrane mucin glycoprotein expressed in mucosal epithelial cells and hematopoietic cells. MUC1 is involved in the resolution of inflammation during airway Pseudomonas aeruginosa (Pa) infection by suppressing Toll-like receptor signaling in airway epithelial cells. Although alveolar macrophages are recognized as critical mediators of cell-mediated immunity against microorganisms inhaled into the airways, the role of MUC1 in regulating their response is unknown. The aims of this study were to determine whether macrophages express MUC1, and, if so, whether MUC1 expression might be associated with macrophage M0/M1/M2 differentiation or phagocytic activity. Human and mouse MUC1/Muc1 expression was drastically up-regulated in classically activated (M1) macrophages compared with nonactivated (M0) and alternatively activated (M2) macrophages. M1 polarization and Pa stimulation each increased MUC1 ectodomain shedding from the macrophage surface in a TNF-a-converting enzyme-dependent manner. MUC1/Muc1 deficiency in M0 macrophages increased adhesion and phagocytosis of Pa and Escherichia coli compared with MUC1/Muc1-expressing cells, and attenuation of phagocytosis by MUC1 was augmented after polarization into M1 macrophages compared with M0 macrophages. Finally, MUC1/Muc1 deficiency in macrophages increased reactive oxygen species production and TNF-a release in response to Pa compared with MUC1/Muc1-sufficient cells. These results indicate that MUC1/Muc1 expression by macrophages is predominantly in the M1 subtype, and that MUC1/Muc1 expression in these cells decreases their phagocytic activity in an antiinflammatory manner.

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“…MUC16 is the largest of the three and is the largest cell surface glycoprotein known. The ectodomain has a massive (12,000 amino acid) O-glycosylated domain, a tandem repeat domain consisting of more than 60 repeats of 156 amino acids, and S perm-E nterokinase-A grin (SEA) domains (O'Brien et al 2001 ;Yin and Lloyd 2001 ;Gipson et al 2014 ). Indirect evidence for the occurrence of MUC16 splice variants has been suggested [discussed in Haridas et al ( 2014 )]; however, mRNA splice variants have not been rigorously identifi ed.…”

Section: Structurementioning

confidence: 99%

Transmembrane Mucin Expression and Function in Embryo Implantation and Placentation

Constantinou

Morgado

Carson

2015

Advances in Anatomy, Embryology and Cell Biology

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Transmembrane mucins (TMs) are extremely large, complex glycoproteins that line the apical surfaces of simple epithelia including those of the female reproductive tract. TMs provide a physical barrier consistent with their role as part of the innate immune system. This barrier function must be overcome in the context of embryo implantation to permit blastocyst attachment. Three major TMs have been identified in uterine epithelia of multiple species: MUC1, MUC4, and MUC16. MUC1 has been found in all species studied to date, whereas expression of MUC4 and MUC16 have been less well studied and may be species specific. The strategies for removing mucins to permit embryo attachment also vary in a species-specific way and include both hormonal suppression of TM gene expression and membrane clearance via cell surface proteases. Studies emerging from the cancer literature indicate that TMs can modulate a surprisingly wide variety of signal transduction processes. Furthermore, various cell surface proteins have been identified that bind either the oligosaccharide or protein motifs of TMs suggesting that these molecules may support cell attachment in some contexts, including trophoblast interactions with cells of the immune system. The intimate association of TMs at sites of embryo-maternal interaction and the varied functions these complex molecules can play make them key players in embryo implantation and placentation processes.

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Comparison of the Transmembrane Mucins MUC1 and MUC16 in Epithelial Barrier Function

Cited by 105 publications

References 47 publications

Human conjunctival goblet cells express the membrane associated mucin MUC16: Localization to mucin granules

Human conjunctival goblet cells express the membrane associated mucin MUC16: Localization to mucin granules

Membrane-Tethered MUC1 Mucin Counter-Regulates the Phagocytic Activity of Macrophages

Transmembrane Mucin Expression and Function in Embryo Implantation and Placentation

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