Identification and characterization of CMP-NeuAc:GalNAc-IgA1 alpha2,6-sialyltransferase in IgA1-producing cells.
Glycosylation defects occur in several human diseases. In IgA nephropathy, IgA1 contains O-glycans that are galactose-deficient and consist mostly of core 1 alpha2,6 sialylated N-acetylgalactosamine, a configuration suspected to prevent beta1,3 galactosylation. We confirmed the same aberrancy in IgA1 secreted by the human DAKIKI B cell line. Biochemical assays indicated CMP-NeuAc:GalNAc-IgA1 alpha2,6-sialyltransferase activity in this cell line. However, a candidate enzyme, ST6-GalNAcI, was not transcribed in DAKIKI cells, B cells isolated from blood, or Epstein-Barr virus (EBV)-immortalized IgA1-producing cells from the blood of IgAN patients and healthy controls. Instead, ST6-GalNAcII transcription was detected at a high level. Expression of the ST6-GalNAcII gene and activity of the CMP-NeuAc:GalNAc-IgA1 alpha2,6-sialyltransferase were higher in IgA1-producing cell lines from IgAN patients than in such cells from healthy controls. These data are the first evidence that human cells that lack ST6-GalNAcI can sialylate core 1 GalNAc-Ser/Thr.
Raska
Milan
M
University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Moldoveanu
Zina
Z
Suzuki
Hitoshi
H
Brown
Rhubell
R
Kulhavy
Rose
R
Andrasi
Judit
J
Hall
Stacy
S
Vu
Huong L
HL
Carlsson
Fredric
F
Lindahl
Gunnar
G
Tomana
Milan
M
Julian
Bruce A
BA
Wyatt
Robert J
RJ
Mestecky
Jiri
J
Novak
Jan
J
D002460:Cell Line; D002461:Cell Line, Transformed; D004797:Enzyme-Linked Immunosorbent Assay; D015971:Gene Expression Regulation, Enzymologic; D006031:Glycosylation; D019073:HT29 Cells; D004854:Herpesvirus 4, Human / Q000378:metabolism; D006801:Humans; D007070:Immunoglobulin A / Q000096:biosynthesis*; D037102:Lectins / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000201:enzymology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D048348:Reverse Transcription / Q000235:genetics; D012799:Sialyltransferases / Q000235:genetics / Q000378:metabolism*; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase
D007070:Immunoglobulin A; D037102:Lectins; D012333:RNA, Messenger; C520743:CMP-acetylneuraminyl N-acetylgalactosaminyl-IgA1 alpha2,6-sialyltransferase, human; D012799:Sialyltransferases; C088391:galactosyl-1-3-N-acetylgalactosaminyl-specific 2,6-sialyltransferase; C038525:CMP-N-acetylneuraminate-alpha-N-acetylgalactosaminide alpha-2,6-sialyltransferase; D000094802:beta-D-Galactoside alpha 2-6-Sialyltransferase