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Current Opinion in Chemical Biology Aug 2022Glycosylation, and especially O-linked glycosylation, remains a critical blind spot in the understanding of post-translational modifications. Due to their nature as... (Review)
Review
Glycosylation, and especially O-linked glycosylation, remains a critical blind spot in the understanding of post-translational modifications. Due to their nature as proteins defined by a large density and abundance of O-glycosylation, mucins present extra challenges in the analysis of their structure and function. However, recent breakthroughs in multiple areas of research have rendered mucin-domain glycoproteins more accessible to current characterization techniques. In particular, the adaptation of mucinases to glycoproteomic workflows, the manipulation of cellular glycosylation pathways, and the advances in synthetic methods to more closely mimic mucin domains have introduced new and exciting avenues to study mucin glycoproteins. Here, we summarize recent developments in understanding the structure and biological function of mucin domains and their associated glycans, from glycoproteomic tools and visualization methods to synthetic glycopeptide mimetics.
Topics: Glycopeptides; Glycoproteins; Glycosylation; Mucins; Polysaccharides
PubMed: 35752002
DOI: 10.1016/j.cbpa.2022.102174 -
Critical Reviews in Biochemistry and... 1992Considerable advances have been made in recent years in our understanding of the biochemistry of mucin-type glycoproteins. This class of compounds is characterized... (Review)
Review
Considerable advances have been made in recent years in our understanding of the biochemistry of mucin-type glycoproteins. This class of compounds is characterized mainly by a high level of O-linked oligosaccharides. Initially, the glycoproteins were solely known as the major constituents of mucus. Recent studies have shown that mucins from the gastrointestinal tract, lungs, salivary glands, sweat glands, breast, and tumor cells are structurally related to high-molecular-weight glycoproteins, which are produced by epithelial cells as membrane proteins. During mucin synthesis, an orchestrated sequence of events results in giant molecules of Mr 4 to 6 x 10(6), which are stored in mucous granules until secretion. Once secreted, mucin forms a barrier, not only to protect the delicate epithelial cells against the extracellular environment, but also to select substances for binding and uptake by these epithelia. This review is designed to critically examine relations between structure and function of the different compounds categorized as mucin glycoproteins.
Topics: Amino Acid Sequence; Animals; Carbohydrate Sequence; Humans; Molecular Sequence Data; Mucins; Structure-Activity Relationship
PubMed: 1727693
DOI: 10.3109/10409239209082559 -
ChemPlusChem Dec 2020Mucins are bottlebrush biopolymers that are glycoproteins on the surfaces of cells and as hydrogels secreted inside and outside the body. Mucin function in biology... (Review)
Review
Mucins are bottlebrush biopolymers that are glycoproteins on the surfaces of cells and as hydrogels secreted inside and outside the body. Mucin function in biology includes cell-cell recognition, signaling, protection, adhesion, and lubrication. Because of their attractive and diverse properties, mucins have recently become the focus of synthetic efforts by researchers who hope to understand and emulate these biomaterials. This review is focused on the development of methodologies for preparing mucin-inspired synthetic oligomers and glycopolymers, including solid-phase synthesis, polymerization of glycosylated monomers, and post-polymerization grafting of glycans to polymer chains. How these synthetic mucins have been used in health applications is discussed. Natural mucins are formed from a conserved set of monomers that are combined into chains of different sequences and lengths to achieve materials with widely diverse properties. Adopting this design paradigm from natural mucins could lead to next-generation bioinspired synthetic materials.
Topics: Humans; Mucins; Polymers
PubMed: 33346954
DOI: 10.1002/cplu.202000637 -
Advanced Drug Delivery Reviews Dec 2022Mucin glycoproteins are the major component of mucus and coat epithelial cell surfaces forming the glycocalyx. The glycocalyx and mucus are involved in the transport of... (Review)
Review
Mucin glycoproteins are the major component of mucus and coat epithelial cell surfaces forming the glycocalyx. The glycocalyx and mucus are involved in the transport of nutrients, drugs, gases, and pathogens toward the cell surface. Mucins are also involved in diverse diseases such as cystic fibrosis and cancer. Due to inherent heterogeneity in native mucin structure, many synthetic materials have been designed to probe mucin chemistry, biology, and physics. Such materials include various glycopolymers, low molecular weight glycopeptides, glycopolypeptides, polysaccharides, and polysaccharide-protein conjugates. This review highlights advances in the area of design and synthesis of mucin mimic materials, and their biomedical applications in glycan binding, epithelial models of infection, therapeutic delivery, vaccine formulation, and beyond.
Topics: Humans; Mucins; Mucus; Cystic Fibrosis; Polysaccharides; Glycopeptides
PubMed: 36228896
DOI: 10.1016/j.addr.2022.114540 -
Essays in Biochemistry Apr 2023The gut microbiota interacts with the host through the mucus that covers and protects the gastrointestinal epithelium. The main component of the mucus are mucins,... (Review)
Review
The gut microbiota interacts with the host through the mucus that covers and protects the gastrointestinal epithelium. The main component of the mucus are mucins, glycoproteins decorated with hundreds of different O-glycans. Some microbiota members can utilize mucin O-glycans as carbons source. To degrade these host glycans the bacteria express multiple carbohydrate-active enzymes (CAZymes) such as glycoside hydrolases, sulfatases and esterases which are active on specific linkages. The studies of these enzymes in an in vivo context have started to reveal their importance in mucin utilization and gut colonization. It is now clear that bacteria evolved multiple specific CAZymes to overcome the diversity of linkages found in O-glycans. Additionally, changes in mucin degradation by gut microbiota have been associated with diseases like obesity, diabetes, irritable bowel disease and colorectal cancer. Thereby understanding how CAZymes from different bacteria work to degrade mucins is of critical importance to develop new treatments and diagnostics for these increasingly prevalent health problems. This mini-review covers the recent advances in biochemical characterization of mucin O-glycan-degrading CAZymes and how they are connected to human health.
Topics: Humans; Mucins; Gastrointestinal Microbiome; Polysaccharides; Bacteria
PubMed: 36695502
DOI: 10.1042/EBC20220121 -
BMB Reports Jul 2021Mucins are high molecular-weight epithelial glycoproteins and are implicated in many physiological processes, including epithelial cell protection, signaling... (Review)
Review
Mucins are high molecular-weight epithelial glycoproteins and are implicated in many physiological processes, including epithelial cell protection, signaling transduction, and tissue homeostasis. Abnormality of mucus expression and structure contributes to biological properties related to human cancer progression. Tumor growth sites induce inhospitable conditions. Many kinds of research suggest that mucins provide a microenvironment to avoid hypoxia, acidic, and other biological conditions that promote cancer progression. Given that the mucus layer captures growth factors or cytokines, we propose that mucin helps to ameliorate inhospitable conditions in tumor-growing sites. Additionally, the composition and structure of mucins enable them to mimic the surface of normal epithelial cells, allowing tumor cells to escape from immune surveillance. Indeed, human cancers such as mucinous carcinoma, show a higher incidence of invasion to adjacent organs and lymph node metastasis than do non-mucinous carcinoma. In this minireview, we discuss how mucin provides a tumor-friendly environment and contributes to increased cancer malignancy in mucinous carcinoma. [BMB Reports 2021; 54(7): 344-355].
Topics: Biomarkers, Tumor; Humans; Mucin-1; Mucins; Neoplasms; Neoplastic Stem Cells; Tumor Microenvironment
PubMed: 34154702
DOI: 10.5483/BMBRep.2021.54.7.064 -
Advanced Drug Delivery Reviews May 2022The secreted mucus layer that lines and protects epithelial cells is conserved across diverse species. While the exact composition of this protective layer varies... (Review)
Review
The secreted mucus layer that lines and protects epithelial cells is conserved across diverse species. While the exact composition of this protective layer varies between organisms, certain elements are conserved, including proteins that are heavily decorated with N-acetylgalactosamine-based sugars linked to serines or threonines (O-linked glycosylation). These heavily O-glycosylated proteins, known as mucins, exist in many forms and are able to form hydrated gel-like structures that coat epithelial surfaces. In vivo studies in diverse organisms have highlighted the importance of both the mucin proteins as well as their constituent O-glycans in the protection and health of internal epithelia. Here, we summarize in vivo approaches that have shed light on the synthesis and function of these essential components of mucus.
Topics: Epithelial Cells; Glycosylation; Humans; Mucins; Mucus; Polysaccharides
PubMed: 35278522
DOI: 10.1016/j.addr.2022.114182 -
Journal of Cutaneous Pathology Nov 2016Mucins are high-molecular weight glycoproteins typically found in normal skin in small amounts. There are several reports regarding different types of cutaneous... (Review)
Review
Mucins are high-molecular weight glycoproteins typically found in normal skin in small amounts. There are several reports regarding different types of cutaneous mucinosis. In this report, we discuss mucins in dermatopathology as a diagnostic clue of some well-known entities and some less frequent cutaneous diseases. We also emphasize mucin as a sign in the differential diagnosis between conditions that show histopathological overlap. Lastly, we discuss the locations and circumstances in which mucin could be considered almost normal or physiological.
Topics: Diagnosis, Differential; Humans; Immunohistochemistry; Mucins; Skin Diseases
PubMed: 27500958
DOI: 10.1111/cup.12782 -
Annual Review of Physiology 1995
Review
Topics: Animals; Diffusion; Epithelium; Gastric Mucins; Hydrogen-Ion Concentration; Magnetic Resonance Spectroscopy; Mucins; Peptides; Scattering, Radiation; Ultracentrifugation; Viscosity
PubMed: 7778881
DOI: 10.1146/annurev.ph.57.030195.003223 -
Advances in Cancer Research 2023Mucin-domain glycoproteins are highly O-glycosylated cell surface and secreted proteins that serve as both biochemical and biophysical modulators. Aberrant expression... (Review)
Review
Mucin-domain glycoproteins are highly O-glycosylated cell surface and secreted proteins that serve as both biochemical and biophysical modulators. Aberrant expression and glycosylation of mucins are known hallmarks in numerous malignancies, yet mucin-domain glycoproteins remain enigmatic in the broad landscape of cancer glycobiology. Here we review the multifaceted roles of mucins in cancer through the lens of the analytical and biochemical methods used to study them. We also describe a collection of emerging tools that are specifically equipped to characterize mucin-domain glycoproteins in complex biological backgrounds. These approaches are poised to further elucidate how mucin biology can be understood and subsequently targeted for the next generation of cancer therapeutics.
Topics: Humans; Mucins; Glycoproteins; Neoplasms; Glycosylation
PubMed: 36725114
DOI: 10.1016/bs.acr.2022.09.001