TY - JOUR
T1 - Initiation of protein O glycosylation by the polypeptide GalNAcT-1 in vascular biology and humoral immunity
AU - Tenno, Mari
AU - Ohtsubo, Kazuaki
AU - Hagen, Fred K.
AU - Ditto, David
AU - Zarbock, Alexander
AU - Schaerli, Patrick
AU - Von Andrian, Ulrich H.
AU - Ley, Klaus
AU - Le, Dzung
AU - Tabak, Lawrence A.
AU - Marth, Jamey D.
PY - 2007/12
Y1 - 2007/12
N2 - Core-type protein O glycosylation is initiated by polypeptide N-acetylgalactosamine (GalNAc) transferase (ppGalNAcT) activity and produces the covalent linkage of serine and threonine residues of proteins. More than a dozen ppGalNAcTs operate within multicellular organisms, and they differ with respect to expression patterns and substrate selectivity. These distinctive features imply that each ppGalNAcT may differentially modulate regulatory processes in animal development, physiology, and perhaps disease. We found that ppGal NAcT-1 plays key roles in cell and glycoprotein selective functions that modulate the hematopoietic system. Loss of ppGalNAcT-1 activity in the mouse results in a bleeding disorder which tracks with reduced plasma levels of blood coagulation factors V, VII, VIII, IX, X, and XII. ppGalNAcT-1 further supports leukocyte trafficking and residency in normal homeostatic physiology as well as during inflammatory responses, in part by providing a scaffold for the synthesis of selectin ligands expressed by neutrophils and endothelial cells of peripheral lymph nodes. Animals lacking ppGalNAcT-1 are also markedly impaired in immunoglobulin G production, coincident with increased germinal center B-cell apoptosis and reduced levels of plasma B cells. These findings reveal that the initiation of protein O glycosylation by ppGal NAcT-1 provides a distinctive repertoire of advantageous functions that support vascular responses and humoral immunity.
AB - Core-type protein O glycosylation is initiated by polypeptide N-acetylgalactosamine (GalNAc) transferase (ppGalNAcT) activity and produces the covalent linkage of serine and threonine residues of proteins. More than a dozen ppGalNAcTs operate within multicellular organisms, and they differ with respect to expression patterns and substrate selectivity. These distinctive features imply that each ppGalNAcT may differentially modulate regulatory processes in animal development, physiology, and perhaps disease. We found that ppGal NAcT-1 plays key roles in cell and glycoprotein selective functions that modulate the hematopoietic system. Loss of ppGalNAcT-1 activity in the mouse results in a bleeding disorder which tracks with reduced plasma levels of blood coagulation factors V, VII, VIII, IX, X, and XII. ppGalNAcT-1 further supports leukocyte trafficking and residency in normal homeostatic physiology as well as during inflammatory responses, in part by providing a scaffold for the synthesis of selectin ligands expressed by neutrophils and endothelial cells of peripheral lymph nodes. Animals lacking ppGalNAcT-1 are also markedly impaired in immunoglobulin G production, coincident with increased germinal center B-cell apoptosis and reduced levels of plasma B cells. These findings reveal that the initiation of protein O glycosylation by ppGal NAcT-1 provides a distinctive repertoire of advantageous functions that support vascular responses and humoral immunity.
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U2 - 10.1128/MCB.01204-07
DO - 10.1128/MCB.01204-07
M3 - Article
C2 - 17923703
AN - SCOPUS:37549057604
SN - 0270-7306
VL - 27
SP - 8783
EP - 8796
JO - Molecular and Cellular Biology
JF - Molecular and Cellular Biology
IS - 24
ER -