Cellular and Molecular Biology of Airway Mucins

Abstract

Airway mucus constitutes a thin layer of airway surface liquid with component macromolecules that covers the luminal surface of the respiratory tract. The major function of mucus is to protect the lungs through mucociliary clearance of inhaled foreign particles and noxious chemicals. Mucus is comprised of water, ions, mucin glycoproteins, and a variety of other macromolecules, some of which possess anti-microbial, anti-protease, and anti-oxidant activities. Mucins comprise the major protein component of mucus and exist as secreted and cell-associated glycoproteins. Secreted, gel-forming mucins are mainly responsible for the viscoelastic property of mucus, which is crucial for effective mucociliary clearance. Cell-associated mucins shield the epithelial surface from pathogens through their extracellular domains and regulate intracellular signaling through their cytoplasmic regions. However, neither the exact structures of mucin glycoproteins, nor the manner through which their expression is regulated, are completely understood. This chapter reviews what is currently known about the cellular and molecular properties of airway mucins.

NEU1 Sialidase Regulates Membrane-tethered Mucin (MUC1) Ectodomain Adhesiveness for Pseudomonas aeruginosa and Decoy Receptor Release

“…This extended rod-like conformation allows MUC1 to protrude higher than most membrane-associated proteins above the EC surface where it is strategically positioned to interact with P. aeruginosa in the airway lumen. The degree of MUC1 extension into the lumen depends upon the number of tandem repeat units, a genetically inherited allelic polymorphism varying from 20 to 120 repeats (13). Whether upon desialylation, MUC1 molecules with more tandem repeats exhibit greater adhesiveness for P. aeruginosa and/or superior decoy receptor function, or whether individuals expressing different repeat numbers have altered susceptibility to invasive P. aeruginosa lung infection, is unknown.…”

“…P. aeruginosa flagellin engages Toll-like receptor (TLR) 5 (11) and the transmembrane mucin 1 (MUC1) (12), and each receptor-ligand interaction is coupled to intracellular signaling. MUC1 consists of a Ͼ250-kDa ectodomain (ED), with a variable number of highly sialylated tandem repeats, which is proteolytically processed and shed from the EC surface (13). Three MUC1 sheddases have been identified, including matrix metalloproteinase (MMP) 14, a disintegrin and metalloproteinase (ADAM) 17, and ␥-secretase (14 -16).…”

Gel-forming mucins form distinct morphologic structures in airways

“…These gel-forming mucins are long, heavily glycosylated proteins with similar domain organization and amino acid sequence. Previous studies described biochemical properties of these and related mucins (1,4,6,8). In human airways, MUC5B is produced in submucosal glands and goblet cells, and MUC5AC is produced in goblet cells (1,4,5,9).…”

The Caenorhabditis elegans Excretory System: A Model for Tubulogenesis, Cell Fate Specification, and Plasticity

“…ZP proteins form fibrils and contribute to many apical matrices (Plaza et al 2010), including luminal matrices of the Drosophila tracheal system (Jazwinska et al 2003), mammalian vascular system (Govani and Shovlin 2009), and kidney (Rampoldi et al 2011). Mucins form gel-like protective barriers within many tubular epithelia (Johansson et al 2013;Lillehoj et al 2013). LET-653 is one key component of the early luminal matrix in the duct and pore (H. Gill, J. Cohen and M. Sundaram, unpublished results).…”