All in the family: the UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferases

Hagen, Karl S.; Fritz, Timothy A.; Tabak, Lawrence A.

doi:10.1093/glycob/cwg007

Cited by 450 publications

(260 citation statements)

References 117 publications

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“…GALNT3 codes for the widely expressed ppGalNacT3 glycosyltransferase (Ten Hagen et al 2003). The mechanisms underlying the role of ppGalNacT3 in maintaining phosphate homeostasis are still elusive.…”

Section: Discussionmentioning

confidence: 99%

“…It is often associated with hyperphosphatemia (Smack et al 1996), and is then termed hyperphosphatemic familial tumoral calcinosis (HFTC; MIM211900). HFTC has been shown to result from loss-of-function mutations in at least two genes: GAL-NT3 coding for UDP-N-acetyl-alpha-D-galactosamine: polypeptide n-acetylgalactosaminyltransferase 3 (ppGalNacT3) (Topaz et al 2004;Ichikawa et al 2005), a glycosyltransferase, which initiates O-glycosylation (Ten Hagen et al 2003);and FGF23 (Benet-Page`s et al 2005;Larsson et al 2005;Araya et al 2005;Chefetz et al 2005) coding for fibroblast growth factor 23 (FGF23), a potent phosphaturic protein (Berndt et al 2005).…”

Section: Introductionmentioning

confidence: 99%

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Hyperphosphatemic familial tumoral calcinosis caused by a mutation in GALNT3 in a European kindred

et al. 2006

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Hyperphosphatemic familial tumoral calcinosis (HFTC) is an autosomal recessive metabolic disorder characterized by extensive phenotypic and genetic heterogeneity. HFTC was shown recently to result from mutations in two genes: GALNT3, coding for a glycosyltransferase responsible for initiating O-glycosylation, and FGF23, coding for a potent phosphaturic protein.All GALNT3 mutations reported so far have been identified in patients of either Middle Eastern or African-American extraction, corroborating numerous historical reports of the disorder in Africa and in the Middle East. In the present study, we describe a patient of Northern European origin displaying typical features of HFTC. Mutation analysis revealed that this patient carries a homozygous novel nonsense mutation in GALNT3 predicted to result in the synthesis of a significantly truncated protein. The present results expand the spectrum of known mutations in GALNT3 and demonstrate the existence of HFTC-causing mutations in this gene outside the Middle Eastern and AfricanAmerican populations.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Hyperphosphatemic familial tumoral calcinosis caused by a mutation in GALNT3 in a European kindred

et al. 2006

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“…Mucin type O-GalNAc glycosylation is initiated by the action of a family of polypeptide GalNActransferases localized in the cis-Golgi apparatus [52] (Fig. 4).…”

Section: Polypeptide Galnac-transferase-3mentioning

confidence: 99%

Diseases of glycosylation beyond classical congenital disorders of glycosylation

Hennet

2012

Biochimica et Biophysica Acta (BBA) - General Subjects

117

103

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BACKGROUND: Diseases of glycosylation are rare inherited disorders, which are often referred to as congenital disorders of glycosylation (CDG). Several types of CDG have been described in the last decades, encompassing defects of nucleotide-sugar biosynthesis, nucleotide-sugar transporters, glycosyltransferases and vesicular transport. Although clinically heterogeneous, most types of CDG are associated with neurological impairments ranging from severe psychomotor retardation to moderate intellectual disabilities. CDG are mainly caused by defects of N-glycosylation, owing to the simple detection of under-glycosylated serum transferrin by isoelectric focusing. SCOPE OF REVIEW: In the last years, several disorders of O-glycosylation, glycolipid and glycosaminoglycan biosynthesis have been described, which are known by trivial names not directly associated with the family of CDG. The present review outlines 64 gene defects affecting glycan biosynthesis and modifications, thereby underlining the complexity of glycosylation pathways and pointing to unexpected phenotypes and functional redundancies in the control of glycoconjugate biosynthesis. MAJOR CONCLUSIONS: The increasing application of whole-genome sequencing techniques unravels new defects of glycosylation, which are associated to moderate forms of mental disabilities. GENERAL SIGNIFICANCE: The knowledge gathered through the investigation of CDG increases the understanding of the functions associated to protein glycosylation in humans. This article is part of a Special Issue entitled Glycoproteomics.

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confidence: 99%

“…This enzymatic step is catalyzed by a polypeptide GalNAc transferase (ppGalNAcT) and is followed by the attachment of other saccharide linkages to this GalNAc by other enzymes in the Golgi apparatus (21,22). More than a dozen ppGalNAcTs have been identified, and the isozymes differ with respect to expression patterns and substrate selectivity (21). Surprisingly, genetic elimination of ppGalNAcT-1 in the mouse did not abolish Oglycan formation in vivo (23,24), indicating at least partially redundant functions of the different ppGalNAcT isoforms (24,25).…”

mentioning

confidence: 99%

Severe Impairment of Leukocyte Recruitment in ppGalNAcT-1–Deficient Mice

Block

Ley

Zarbock

2012

The Journal of Immunology

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P-selectin glycoprotein ligand-1 plays an important role in leukocyte recruitment. Its binding affinity to selectins is modulated by posttranslational modifications. The polypeptide N-acetylgalactosamine transferase-1 (ppGalNAcT-1) initiates core-type protein O-glycosylation. To address whether the glycosylation of P-selectin glycoprotein ligand-1 by ppGalNAcT-1 is important for leukocyte recruitment in vivo, we investigated leukocyte recruitment in untreated and TNF-α–treated cremaster muscles comparing ppGalNAcT-1–deficient mice (Galnt1−/−) and wild-type mice. In untreated and TNF-α–treated Galnt1−/− mice, leukocyte rolling, adhesion, and transmigration were significantly reduced, with markedly increased rolling velocity compared with control mice. L-selectin–dependent leukocyte rolling was completely abolished in Galnt1−/− mice compared with wild-type mice. Thioglycollate-induced peritonitis experiments with chimeric mice revealed that hematopoietic ppGalNAcT-1 is important for leukocyte recruitment. These data show that the loss of ppGalNAcT-1 led to reduced leukocyte rolling and recruitment and increased rolling velocity, suggesting a predominant role for ppGalNAcT-1 in attaching functionally relevant O-linked glycans to selectin ligands.

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All in the family: the UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferases

Cited by 450 publications

References 117 publications

Hyperphosphatemic familial tumoral calcinosis caused by a mutation in GALNT3 in a European kindred

Hyperphosphatemic familial tumoral calcinosis caused by a mutation in GALNT3 in a European kindred

Diseases of glycosylation beyond classical congenital disorders of glycosylation

Severe Impairment of Leukocyte Recruitment in ppGalNAcT-1–Deficient Mice

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