Mucins are a family of large, heavily glycosylated proteins that form primary protective barriers throughout the body. They are found in various secretions and on epithelial surfaces, including the respiratory, gastrointestinal, and reproductive tracts, eyes, and mouth.
The primary role of mucins is to form mucus, a slippery, protective layer. This layer acts as a physical barrier, shielding underlying cells from mechanical stress, harmful substances, and pathogens. Mucus also facilitates lubrication, aiding smooth movement and protection.
The Fundamental Building Blocks
Mucins are classified as glycoproteins, meaning they are composed of both protein and carbohydrate components. The core of a mucin molecule is a protein backbone, often referred to as an apomucin. This protein backbone is synthesized first within the cell.
Numerous sugar chains are attached to this apomucin core through O-glycosylation. This extensive glycosylation means a significant portion of the mucin’s mass is carbohydrate. Common sugars include N-acetylgalactosamine, fucose, galactose, and sialic acid, which contribute to the mucin’s structure and function.
Assembling the Mucin Network
Individual mucin molecules polymerize to form larger, functional structures. Mucin monomers link end-to-end, creating long, flexible polymers. This linkage depends on disulfide bonds.
Disulfide bonds form between cysteine-rich regions at the N- and C-termini of mucin monomers, connecting individual units into extended chains. These long mucin polymers then intertwine and cross-link.
This intertwining and cross-linking forms the characteristic viscous, gel-like network known as mucus. This network provides the physical and protective properties of mucus in the body.
Diversity in Mucin Structures
The term “mucin” refers to a diverse family of related glycoproteins, each with distinct structural characteristics. Differences arise from variations in their protein core sequences, encoded by different mucin genes like MUC1, MUC2, MUC5AC, MUC5B, MUC6, and MUC7.
Beyond the protein core, mucins exhibit diverse glycosylation patterns, including variations in the types, lengths, and branching of their sugar chains. These carbohydrate modifications influence the mucin’s size, shape, and polymeric organization. Some mucins are secreted into the lumen, while others remain tethered to cell membranes.
These structural distinctions dictate their specific locations in the body and their specialized functions. For example, secreted mucins like MUC2 and MUC5AC form dense protective barriers in the gut and airways, respectively. In contrast, membrane-bound mucins, such as MUC1, play roles in cell signaling and lubrication on epithelial surfaces.
Mucin Structure in Health and Disease
Alterations in mucin structure impact human health. Changes in glycosylation patterns are observed in cancer, influencing cell adhesion, promoting metastasis, and helping cancer cells evade the immune system. These altered sugar chains can serve as disease progression markers.
In cystic fibrosis, disruptions in mucin production or polymerization lead to abnormally thick, sticky mucus, particularly due to changes in MUC5B and MUC5AC. This altered structure impedes mucociliary clearance in the airways, trapping bacteria and leading to chronic infections and inflammation.
Altered mucin structure also plays a role in inflammatory bowel diseases like ulcerative colitis and Crohn’s disease, where changes in MUC2 barrier function are observed. A compromised mucin barrier can lead to increased intestinal lining permeability, allowing bacteria and inflammatory agents to penetrate and exacerbate inflammation. Understanding these structural changes provides insights into disease mechanisms and potential therapeutic targets.