Mucin Biophysics

Bansil, Rama; Stanley, E; LaMont, J. Thomas

doi:10.1146/annurev.ph.57.030195.003223

Cited by 344 publications

(320 citation statements)

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“…Yet levels of Fas at the B-cell surface were normal in ppGalNAcT-1 deficiency, and no alterations in the expression of other cell surface glycoproteins were as yet detected (data The initiation of protein O glycosylation in vivo by ppGal NAcT-1 translates into vital roles in vascular biology, hemostasis, and humoral immunity. Core-type protein O glycosylation is generally known to support mucin structure and function on endothelial cell surfaces, protecting cells against stress and pathogen infection (3,51). Furthermore, it was recently shown that a loss of core 3 O-glycans in mice increases their susceptibility to colitis and colorectal tumors (1).…”

Section: Germ Line Mutagenesis Of Polypeptide Galnact-1 Disrupts O-glmentioning

confidence: 99%

Initiation of Protein O Glycosylation by the Polypeptide GalNAcT-1 in Vascular Biology and Humoral Immunity

Tenno

Ohtsubo

Hagen

et al. 2007

Molecular and Cellular Biology

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Core-type protein O glycosylation is initiated by polypeptide N-acetylgalactosamine (GalNAc) transferase (ppGalNAcT) activity and produces the covalent linkage of serine and threonine residues of proteins. More than a dozen ppGalNAcTs operate within multicellular organisms, and they differ with respect to expression patterns and substrate selectivity. These distinctive features imply that each ppGalNAcT may differentially modulate regulatory processes in animal development, physiology, and perhaps disease. We found that ppGal NAcT-1 plays key roles in cell and glycoprotein selective functions that modulate the hematopoietic system. Loss of ppGalNAcT-1 activity in the mouse results in a bleeding disorder which tracks with reduced plasma levels of blood coagulation factors V, VII, VIII, IX, X, and XII. ppGalNAcT-1 further supports leukocyte trafficking and residency in normal homeostatic physiology as well as during inflammatory responses, in part by providing a scaffold for the synthesis of selectin ligands expressed by neutrophils and endothelial cells of peripheral lymph nodes. Animals lacking ppGalNAcT-1 are also markedly impaired in immunoglobulin G production, coincident with increased germinal center B-cell apoptosis and reduced levels of plasma B cells. These findings reveal that the initiation of protein O glycosylation by ppGal NAcT-1 provides a distinctive repertoire of advantageous functions that support vascular responses and humoral immunity.

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Section: Germ Line Mutagenesis Of Polypeptide Galnact-1 Disrupts O-glmentioning

confidence: 99%

Initiation of Protein O Glycosylation by the Polypeptide GalNAcT-1 in Vascular Biology and Humoral Immunity

Tenno

Ohtsubo

Hagen

et al. 2007

Molecular and Cellular Biology

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“…Mucins constitute a family of high molecular mass glycoproteins synthesized by the goblet cells of the epithelia and in some cases by submucosal glands (for more complete reviews, see Refs. [1][2][3].…”

mentioning

confidence: 99%

Genomic Organization of the 3′ Region of the Human Mucin GeneMUC5B

Desseyn¹,

Aubert²,

Seuningen³

et al. 1997

Journal of Biological Chemistry

115

102

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MUC5B, mapped clustered with MUC6, MUC2, and MUC5AC to chromosome 11p15.5, is a human mucin gene of which the genomic organization is being elucidated. We have recently published the sequence and the peptide organization of its huge central exon, 10,713 base pairs (bp) in length. We present here the genomic organization of its 3 region, which encompasses 10,690 bp. The genomic sequence has been completely determined. The 3 region of MUC5B is composed of 18 exons ranging in size from 32 to 781 bp, contrasting thus with the very large central exon. The sizes of the 18 introns range from 114 to 1118 bp. Some repetitive sequences were identified in four introns. The peptide deduced from the sequence of the 18 exons consists of an 808-amino acid peptide. This carboxyl-terminal region exhibits extensive sequence similarity to MUC2, MUC5AC, and von Willebrand factor, particularly the number and the positions of the cysteine residues, suggesting that this domain may be derived from a common ancestral gene. The presence in these components of a cystine knot also found in growth factors such as transforming growth factor-␤ is of particular interest. Moreover, one part of this peptide is identical to the 196-amino acid sequence deduced from the cDNA clone pSM2-1, which codes for a part of the high molecular weight mucin MG1 isolated from human sublingual gland. Considering the expression pattern of MUC5B and the origin of MG1, we can thus conclude that MUC5B encodes MG1.Mucus is the layer that covers, protects, and lubricates the luminal surfaces of epithelial respiratory, gastrointestinal, and reproductive tracts. These basic properties are due to the viscous and viscoelastic properties of mucins, the major glycoprotein components of mucus. Mucins constitute a family of high molecular mass glycoproteins synthesized by the goblet cells of the epithelia and in some cases by submucosal glands (for more complete reviews, see Refs. 1-3).Alterations of the biosynthesis of mucins affecting the protein core and/or the carbohydrate content linked to the peptide have been observed in numerous pathological situations such as various adenomas and carcinomas, inflammatory diseases such as cystic fibrosis, asthma, chronic bronchitis, or inflammatory bowel diseases (4 -7). Moreover, the hypersecretion of mucins and the presence of alternating hydrophobic and hydrophilic domains in mucins have been shown to play a central role in the pathogenesis of cholesterol gallstones (8, 9).All apomucins contain tandemly repeated sequences rich in threonine and/or serine. Due to the high carbohydrate content, the peptide moiety of mucins has been difficult to characterize. cDNA cloning has enabled researchers to approach the study of the mucins over the past decade. Today, the membrane-associated mucin MUC1 and the secreted MUC7 are the only mucins for which the full-length cDNA and the genomic organization have been reported (10 -13). Both were revealed to be, in fact, small mucins. A complete cDNA of the large secreted mucin MUC2 (14 -17) has been...

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“…Upon release, phase transition mainly driven by the Donnan effect triggers the massive decondensation of mucin networks. Hydrogen bonding, hydrophilic and hydrophobic interactions have also been proposed to contribute to the gel properties of mucin The gel characteristics and rheological properties of mucin are critical for the maintainance the integrity of epithelia by trapping bacteria and viruses and for mucociliary clearance (Bansil & Stanley, 1995;Verdugo, 1990).…”

Section: Mucus Rheological Propertiesmentioning

confidence: 99%