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β1,4-galactosyltransferase 1 is a novel receptor for IgA in human mesangial cells
journal contribution
posted on 2018-02-09, 14:20 authored by Karen Molyneux, David Wimbury, Izabella Pawluczyk, Masahiro Muto, Jasraj Bhachu, Peter R. Mertens, John Feehally, Jonathan BarrattIgA nephropathy is characterized by mesangial deposition of IgA, mesangial cell proliferation, and extracellular matrix production. Mesangial cells bind IgA, but the identity of all potential receptors involved remains incomplete. The transferrin receptor (CD71) acts as a mesangial cell IgA receptor and its expression is upregulated in many forms of glomerulonephritis, including IgA nephropathy. CD71 is not expressed in healthy glomeruli and blocking CD71 does not completely abrogate mesangial cell IgA binding. Previously we showed that mesangial cells express a receptor that binds the Fc portion of IgA and now report that this receptor is an isoform of β-1,4-galactosyltransferase. A human mesangial cell cDNA library was screened for IgA binding proteins and β-1,4-galactosyltransferase identified. Cell surface expression of the long isoform of β-1,4-galactosyltransferase was shown by flow cytometry and confocal microscopy and confirmed by immunoblotting. Glomerular β-1,4-galactosyltransferase expression was increased in IgA nephropathy. IgA binding and IgA-induced mesangial cell phosphorylation of spleen tyrosine kinase and IL-6 synthesis were inhibited by a panel of β-1,4-galactosyltransferase-specific antibodies, suggesting IgA binds to the catalytic domain of β-1,4-galactosyltransferase. Thus, β-1,4-galactosyltransferase is a constitutively expressed mesangial cell IgA receptor with an important role in both mesangial IgA clearance and the initial response to IgA deposition.
History
Citation
Kidney International, 2017, 92 (6), pp. 1458-1468Author affiliation
/Organisation/COLLEGE OF LIFE SCIENCES/School of Medicine/Department of Infection, Immunity and InflammationVersion
- AM (Accepted Manuscript)
Published in
Kidney InternationalPublisher
Elsevier for International Society of Nephrologyissn
0085-2538eissn
1523-1755Acceptance date
2017-05-11Copyright date
2017Available date
2018-07-24Publisher DOI
Publisher version
https://www.sciencedirect.com/science/article/pii/S0085253817303253?via=ihubNotes
The file associated with this record is under embargo until 12 months after publication, in accordance with the publisher's self-archiving policy. The full text may be available through the publisher links provided above.Language
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