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β1,4-galactosyltransferase 1 is a novel receptor for IgA in human mesangial cells

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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 Barratt
IgA 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. 1458-1468

Author affiliation

/Organisation/COLLEGE OF LIFE SCIENCES/School of Medicine/Department of Infection, Immunity and Inflammation

Version

  • AM (Accepted Manuscript)

Published in

Kidney International

Publisher

Elsevier for International Society of Nephrology

issn

0085-2538

eissn

1523-1755

Acceptance date

2017-05-11

Copyright date

2017

Available date

2018-07-24

Publisher version

https://www.sciencedirect.com/science/article/pii/S0085253817303253?via=ihub

Notes

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

en

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