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Discuss O-linked oligosaccharide decoration of proteins in the production of mucus and its implications in mucus-producing adeno - Essay Example

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Mucin-type O glycans is a component of the outermost coating of all cell surfaces. Aside from providing protective barrier and support, these molecules mediate adhesions to other cells or extracellular matrix. These are made by glycosyltransferases (Tabak, 2010)…
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Discuss O-linked oligosaccharide decoration of proteins in the production of mucus and its implications in mucus-producing adeno
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Download file to see previous pages These areas in the glycoprotein are aptly called mucin-like domains. Mucin-related proteins can either be membrane-bound, in which case it is enclosing the cell, or secreted to form the extracellular matrix (Tabak, 2010). In the epithelium, such as those on the surface of gastrointestinal wall, O-glyvans attached to epithelial cell membrane-bound mucin and its related proteins, mostly Muc2, constitute what is commonly called mucus. Mucin glycoproteins are made in enormous amounts by a specialized epithelial cell called the goblet cell. Physiologically, this cell is important in producing the inner mucus layer to replace the outer mucus layer used for bacterial clearance. To produce mucus, Muc2 should first be produced and secreted. They are prepared in the Golgi apparatus, in which the proteins are labeled for transport to the surface (Johansson, 2012). They can be compactly stored in large, regulated secretory mucin granules that can be found on the apical cytoplasm of goblet cells (Perez-Vilar, 2007) 2. Importance of mucus Mucus acts as a barrier from injurious elements to which the gut surface is commonly exposed to, such as bacteria and mechanical forces. Microorganisms are trapped by the outer mucus layer for transport and excretion. ...
Defect in mucus production occurs from lack of Muc2 production, Muc2 mutation, or inhibition of glucosyltransferases. Without mucus, bacteria attaches to the epithelium, increases intestinal permeability, and raises risk for colitis (Kim and Ho, 2010). Aside from the gastrointestinal systems, mucus also has a protective function in the respiratory, urogenital, ophalmologic, and auditory systems. Deregulation of its production or composition is implicated in chronic airway diseases, such as chronic obstructive pulmonary disease, asthma, and cystic fibrosis (Perez-Vilar, 2007). In cystic fibrosis, the alkalization due to the defective intracellular chloride channel caused defects in pH-sensitive glucosyltransferases. The abnormal glycoproteins produced by these defective enzymes also provide receptors for Pseudomonas (Al-Awqati, Barasch, and Landry, 1992). 3. Role in cell signaling The less common O-fucose glycans are attached by O-fucosyltransderase 1 and elongated by ? 1,3N-acetylglucosaminyltransferases to epidermal growth factor-like (EGF) repeats of Notch protein. EGF repeats are approximately 40-amino acid-long cysteine-rich motifs, including a conserved six cysteine span that forms three conserved disulfide bonds. The sugar moiety modulates protein-protein interactions and downstream signaling. Notch is a membrane-bound signaling receptor important in differentiation. Elongation of O-fucose by Fringe limits Notch activation to the dorsal and ventral boundary, since it limits the binding of Notch with its ligands. Fringe defects result to segmentation and somitogenesis defects in mice. Similar to EGF repeats, Thrombospondin tupe 1 repeats (TSR) are made up of six conserved cysteines and three ...Download file to see next pagesRead More
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