O-Glycosylation of a male seminal fluid protein influences sperm binding and female postmating behavior.

Glycoproteins are abundant within the human reproductive system and alterations in glycosylation lead to reproductive disorders, suggesting that glycans play an important role in reproductive function. In this study, we used the reproductive system as a model to investigate the biological functions of O-glycosylation. We found that O-glycosylation in the male accessory glands, an organ responsible for secreting seminal fluid proteins, plays important roles in female postmating behavior.

In vivo mapping of the mouse Galnt3-specific O-glycoproteome.

The UDP-N-acetylgalactosamine polypeptide:N-acetylgalactosaminyltransferase (GalNAc-T) family of enzymes initiates O-linked glycosylation by catalyzing the addition of the first GalNAc sugar to serine or threonine on proteins destined to be membrane-bound or secreted. Defects in individual isoforms of the GalNAc-T family can lead to certain congenital disorders of glycosylation (CDG). The polypeptide N-acetylgalactosaminyltransferase 3 (GALNT)3-CDG, is caused by mutations in GALNT3, resulting in hyperphosphatemic familial tumoral calcinosis due to impaired glycosylation of the phosphate-regulating hormone fibroblast growth factor 23 (FGF23) within osteocytes of the bone.

Loss of the glycosyltransferase Galnt11 affects vitamin D homeostasis and bone composition.

O-glycosylation is a conserved posttranslational modification that impacts many aspects of organismal viability and function. Recent studies examining the glycosyltransferase Galnt11 demonstrated that it glycosylates the endocytic receptor megalin in the kidneys, enabling proper binding and reabsorption of ligands, including vitamin D-binding protein (DBP). Galnt11-deficient mice were unable to properly reabsorb DBP from the urine.

A novel cysteine-rich adaptor protein is required for mucin packaging and secretory granule stability in vivo.

Mucins are large, highly glycosylated extracellular matrix proteins that line and protect epithelia of the respiratory, digestive, and urogenital tracts. Previous work has shown that mucins form large, interconnected polymeric networks that mediate their biological functions once secreted. However, how these large matrix molecules are compacted and packaged into much smaller secretory granules within cells prior to secretion is largely unknown.

Quantitative mapping of the in vivo O-GalNAc glycoproteome in mouse tissues identifies GalNAc-T2 O-glycosites in metabolic disorder.

The family of GalNAc-Ts (GalNAcpolypeptide:N-Acetylgalactosaminyl transferases) catalyzes the first committed step in the synthesis of O-glycans, which is an abundant and biologically important protein modification. Abnormalities in the activity of individual GalNAc-Ts can result in congenital disorders of O-glycosylation (CDG) and influence a broad array of biological functions. How site-specific O-glycans regulate biology is unclear.

Dynamic expression of mucins and the genes controlling mucin-type O-glycosylation within the mouse respiratory system.

The COVID-19 global pandemic has underscored the need to understand how viruses and other pathogens are able to infect and replicate within the respiratory system. Recent studies have highlighted the role of highly O-glycosylated mucins in the protection of the respiratory system as well as how mucin-type O-glycosylation may be able to modify viral infectivity. Therefore, we set out to identify the specific genes controlling mucin-type O-glycosylation throughout the mouse respiratory system as well as determine how their expression and the expression of respiratory mucins is influenced by infection or injury.

Community voices: NIH working toward inclusive excellence by promoting and supporting women in science.

The U. S. National Institutes of Health is committed to addressing gender discrimination and fostering inclusive excellence, which is critical for the advancement of creativity and innovation in science.

A novel role for GalNAc-T2 dependent glycosylation in energy homeostasis.

Objective: GALNT2, encoding polypeptide N-acetylgalactosaminyltransferase 2 (GalNAc-T2), was initially discovered as a regulator of high-density lipoprotein metabolism. GalNAc-T2 is known to exert these effects through post-translational modification, i.e.

In vivo models of mucin biosynthesis and function.

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.

Furin cleavage of the SARS-CoV-2 spike is modulated by -glycosylation.

The SARS-CoV-2 coronavirus responsible for the global pandemic contains a novel furin cleavage site in the spike protein (S) that increases viral infectivity and syncytia formation in cells. Here, we show that -glycosylation near the furin cleavage site is mediated by members of the GALNT enzyme family, resulting in decreased furin cleavage and decreased syncytia formation. Moreover, we show that -glycosylation is dependent on the novel proline at position 681 (P681).

A Cross-Sectional Cohort Study of the Effects of FGF23 Deficiency and Hyperphosphatemia on Dental Structures in Hyperphosphatemic Familial Tumoral Calcinosis.

Hyperphosphatemic familial tumoral calcinosis (HFTC) is a rare autosomal recessive disorder caused by mutations in , , , or FGF23 autoantibodies. Prominent features include high blood phosphate and calcific masses, usually adjacent to large joints. Dental defects have been reported, but not systematically described.

Furin cleavage of the SARS-CoV-2 spike is modulated by O-glycosylation.

The SARS-CoV-2 coronavirus responsible for the global pandemic contains a unique furin cleavage site in the spike protein (S) that increases viral infectivity and syncytia formation. Here, we show that O-glycosylation near the furin cleavage site is mediated by specific members of the GALNT enzyme family and is dependent on the novel proline at position 681 (P681). We further demonstrate that O-glycosylation of S decreases furin cleavage.

Improved online LC-MS/MS identification of O-glycosites by EThcD fragmentation, chemoenzymatic reaction, and SPE enrichment.

O-glycosylation is a highly diverse and complex form of protein post-translational modification. Mucin-type O-glycosylation is initiated by the transfer of N-acetyl-galactosamine (GalNAc) to the hydroxyl group of serine, threonine and tyrosine residues through catalysis by a family of glycosyltransferases, the UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferases (E.C.

Differential splicing of the lectin domain of an -glycosyltransferase modulates both peptide and glycopeptide preferences.

Mucin-type -glycosylation is an essential post-translational modification required for protein secretion, extracellular matrix formation, and organ growth. -Glycosylation is initiated by a large family of enzymes (GALNTs in mammals and PGANTs in ) that catalyze the addition of GalNAc onto the hydroxyl groups of serines or threonines in protein substrates. These enzymes contain two functional domains: a catalytic domain and a C-terminal ricin-like lectin domain comprised of three potential GalNAc recognition repeats termed α, β, and γ.

Loss of the disease-associated glycosyltransferase Galnt3 alters Muc10 glycosylation and the composition of the oral microbiome.

The importance of the microbiome in health and its disruption in disease is continuing to be elucidated. However, the multitude of host and environmental factors that influence the microbiome are still largely unknown. Here, we examined UDP-GalNAc:polypeptide -acetylgalactosaminyltransferase 3 ()-deficient mice, which serve as a model for the disease hyperphosphatemic familial tumoral calcinosis (HFTC).

Galnt11 regulates kidney function by glycosylating the endocytosis receptor megalin to modulate ligand binding.

Chronic kidney disease (CKD) affects more than 20 million Americans and ∼10% of the population worldwide. Genome-wide association studies (GWAS) of kidney functional decline have identified genes associated with CKD, but the precise mechanisms by which they influence kidney function remained largely unexplored. Here, we examine the role of 1 GWAS-identified gene by creating mice deficient for , which encodes a member of the enzyme family that initiates protein O-glycosylation, an essential posttranslational modification known to influence protein function and stability.

Tango1 coordinates the formation of endoplasmic reticulum/Golgi docking sites to mediate secretory granule formation.

Regulated secretion is a conserved process occurring across diverse cells and tissues. Current models suggest that the conserved cargo receptor Tango1 mediates the packaging of collagen into large coat protein complex II (COPII) vesicles that move from the endoplasmic reticulum (ER) to the Golgi apparatus. However, how Tango1 regulates the formation of COPII carriers and influences the secretion of other cargo remains unknown.

Sweet rescue or surrender of the failing heart?

Natriuretic peptides (NPs) are hormones involved in maintaining heart health that undergo proteolytic cleavage to become activated. Previous work has shown that -GalNAc glycans affect their processing and activation. Here, Goetze, Schjoldager, and colleagues now provide comprehensive characterization of -glycosylation of NPs, revealing that all members of the NP family can be modified by -GalNAc glycans.

O-Linked glycosylation in Drosophila melanogaster.

Glycosylation, or the addition of sugars to proteins, is a highly conserved protein modification defined by both the monosaccharide initially added as well as the amino acid to which it is attached. O-Linked glycosylation represents a diverse group of protein modifications occurring on the hydroxyl groups of serine and/or threonine residues. O-Glycosylation can have wide-ranging effects on protein stability and function, which translate into crucial consequences at the organismal level.

A molecular switch orchestrates enzyme specificity and secretory granule morphology.

Regulated secretion is an essential process where molecules destined for export are directed to membranous secretory granules, where they undergo packaging and maturation. Here, we identify a gene (pgant9) that influences the structure and shape of secretory granules within the Drosophila salivary gland. Loss of pgant9, which encodes an O-glycosyltransferase, results in secretory granules with an irregular, shard-like morphology, and altered glycosylation of cargo.

Fostering Strategies to Expand the Consumption of Edible Insects: The Value of a Tripartite Coalition between Academia, Industry, and Government.

Although many insect-based foods are nutritious and often an inexpensive option for human and domesticated animal consumption, there remains a negligible market for such foods in many countries. Several environmental and economic considerations underscore the potential value of insect-based foods, and emerging science suggests that diets incorporating such foods might also convey some genuine health benefits. However, if expanded markets for insect-based foods in cultures naïve to entomophagy are to be pursued, it will be important to develop multifaceted and coordinated strategies to ) delineate authentic health benefits, ) explore means of optimizing insect husbandry and food processing, ) examine cultural barriers to acceptance, ) formulate workable approaches to marketing, and ) address relevant food regulations.

Pleiotropic effects of -glycosylation in colon cancer.

Changes in the -glycosylation of proteins have long been associated with the development of cancer, but establishing causal relationships between altered glycosylation and cancer progression remains incomplete. In this study, the authors perform comparative analyses of the cellular phenotypes, transcriptional changes, and alterations in the glycoproteome in colon cancer cells that differentially express one glycosyltransferase. Their results provide a wealth of data on which future studies can be based.