Unmasking Fucosylation: from Cell Adhesion to Immune System Regulation and Diseases

Abstract

Fucosylation is a biological process broadly observed in vertebrates, invertebrates, plants, bacteria, and fungi. Fucose moieties on cell-surface glycans are increasingly recognized as critical to many cell-cell interaction and signaling processes. One of the characteristic roles of fucose is its regulation of selectin-dependent leukocyte adhesion that has been well studied over the last two decades. Recent studies of fucose in immune cell development and function regulation have significantly expanded the contemporary understanding of fucosylation. From cellular adhesion to immune regulation, herein we discuss the use of gene knockout studies, competitive inhibitors of fucose-containing glycan, and metabolic inhibitors of fucose biosynthesis to probe fucosylated glycan biosynthesis and signaling and its functional consequences. Promising clinical and preclinical applications in sickle cell disease, rheumatoid arthritis, tumor inhibition, metastasis prevention, antibody-dependent cell-mediated cytotoxicity, chemoresistance reversal, and in improving chemotherapy-related side effects and recovery are reviewed.

FUT1 deficiency elicits immune dysregulation and corneal opacity in steady state and under stress

“…Glycans are involved in a wide variety of physiologic and pathologic processes in eukaryotic cells after attachment to proteins or lipids through an enzymatic process called glycosylation 1 . In particular, fucosylated carbohydrates play an important role in the regulation of multiple cellular functions such as cell trafficking, immune cell development, and interaction with gut microbes and are generated through fucosylation mediated by fucosyltransferases (FUTs) [2][3][4] . Thus far, 13 FUT genes have been identified in human genome based on their acceptor specificities and protein sequences 5 .…”

Ion‐Mobility Spectrometry Can Assign Exact Fucosyl Positions in Glycans and Prevent Misinterpretation of Mass‐Spectrometry Data After Gas‐Phase Rearrangement

“…In humans, the structural diversity of fucosylated glycans arises from thirteen fucosyl transferases that, in concert with other glycosyl transferases, create a wide variety of glycan epitopes. Fucosylated epitopes mediate many physiological and disease processes such as leukocyte adhesion during inflammation, fertilization, tissue development, and tumor metastasis . Therefore, the determination of exact fucoside positions and the affirmation of rearrangements are critical for the application of glycans as clinical biomarkers and to understand their biological roles at a molecular level.…”

Chemical Regulation of Glycosylation Processes

“…In this review, the recent approaches for regulation of terminal fucose, poly-N-acetyllatosamine and sialic acid attachment on either N-glycans or O-glycans are discussed briefly. There are several comprehensive reviews for each category reported recently (71)(72)(73). The readers are recommended to these reviews for more detailed information and biomedical interests.…”

“…L-Fucose often exists as a terminal sugar in glycoconjugate glycans that are essential for either physiological or pathological activities, such as inflammation, bacterial and viral infections, tumor metastasis, and genetic disorders (72). Fucosyltransferases (FUTs) catalyze the incorporation of L-fucose residues, a process referred as fucosylation.…”

“…Fucosyltransferases (FUTs) catalyze the incorporation of L-fucose residues, a process referred as fucosylation. Several GDP-fucose analogs have been reported to inhibit FUTs (71,72). However, the charged groups on the GDP portion prevent their uptake into cells and limit their use in biological systems.…”