Identification and characterization of CMP-NeuAc:GalNAc-IgA1 alpha2,6-sialyltransferase in IgA1-producing cells

Summary, in English

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.

• Author: Milan Raska; Zina Moldoveanu; Hitoshi Suzuki; Rhubell Brown; Rose Kulhavy; Judit Andrasi; Stacy Hall; Huong L Vu; Fredric Carlsson; Gunnar Lindahl; Milan Tomana; Bruce A Julian; Robert J Wyatt; Jiri Mestecky; Jan Novak
• Department/s: Division of Medical Microbiology
• Publishing year: 2007
• Language: English
• Pages: 69-78
• Publication/Series: Journal of Molecular Biology
• Volume: 369
• Issue: 1
• Links: http://dx.doi.org/10.1016/j.jmb.2007.03.002
• Document type: Journal article
• Publisher: Elsevier
• Topic: Microbiology in the medical area
• Status: Published
• ISBN/ISSN/Other: ISSN: 1089-8638