N-Acetylglucosamine Functions in Cell Signaling

Abstract

The amino sugar N-acetylglucosamine (GlcNAc) is well known for the important structural roles that it plays at the cell surface. It is a key component of bacterial cell wall peptidoglycan, fungal cell wall chitin, and the extracellular matrix of animal cells. Interestingly, recent studies have also identified new roles for GlcNAc in cell signaling. For example, GlcNAc stimulates the human fungal pathogen Candida albicans to undergo changes in morphogenesis and expression of virulence genes. Pathogenic E. coli responds to GlcNAc by altering the expression of fimbriae and CURLI fibers that promote biofilm formation and GlcNAc stimulates soil bacteria to undergo changes in morphogenesis and production of antibiotics. Studies with animal cells have revealed that GlcNAc influences cell signaling through the posttranslational modification of proteins by glycosylation. O-linked attachment of GlcNAc to Ser and Thr residues regulates a variety of intracellular proteins, including transcription factors such as NFκB, c-myc, and p53. In addition, the specificity of Notch family receptors for different ligands is altered by GlcNAc attachment to fucose residues in the extracellular domain. GlcNAc also impacts signal transduction by altering the degree of branching of N-linked glycans, which influences cell surface signaling proteins. These emerging roles of GlcNAc as an activator and mediator of cellular signaling in fungi, animals, and bacteria will be the focus of this paper.

Regulation of Hyphal Growth and N-Acetylglucosamine Catabolism by Two Transcription Factors in Candida albicans

“…For example, GlcNAc induces hyphal growth in a diverse set of fungi (Kim et al 2000;Gilmore et al 2013), it regulates stress and virulence responses in bacteria, and it can stimulate NLRP3 inflammasome activation in mammalian cells (Konopka 2012;Wolf et al 2016). GlcNAc is commonly found at the extracellular surface of a wide range of cells as a component of bacterial peptidoglycan, fungal cell wall chitin, and mammalian cell glycosaminoglycans (Moussian 2008).…”

High Throughput Screening of Gene Expression for the Investigation of Multifactorial Dermatological Disorders

“…We also found that the hxk1Δ mutant exhibits reduced cytotoxicity compared to the wild type strain of C. albicans, which may be caused by its decreased adherence to the surface of vaginal epithelial cells ( Figures 5 -7). The human extracellular matrix contains a significant amount of GlcNAc [75]. In agreement with a recent review [75], GlcNAc released from the extracellular matrix of human cells during membrane remodeling might explain the induction of C. albicans GlcNAc catabolic genes, such as, NGT1, HXK1, NAG1, and DAC1 ( Figure 4) by vaginal epithelial cells.…”

“…The human extracellular matrix contains a significant amount of GlcNAc [75]. In agreement with a recent review [75], GlcNAc released from the extracellular matrix of human cells during membrane remodeling might explain the induction of C. albicans GlcNAc catabolic genes, such as, NGT1, HXK1, NAG1, and DAC1 ( Figure 4) by vaginal epithelial cells.…”

“…As GlcNAc induces hyphal morphogenesis in C. albicans [75], we sought to monitor the expression of GlcNAc catabolic genes in our in vitro model. Since the RNA-Seq experiment did not provide sufficient number of unique reads for statistical analysis of this group (data not shown), the expression of several GlcNAc catabolic genes was tested by QRT-PCR.…”

“…The GlcNAc biosynthesis plays a key role in chitin biosynthesis [75]. The inner layer of the cell wall of C. albicans consists of chitin (polymers of β-(1,3)-glucan, β-(1,6)-glucan, and GlcNAc).…”