PLA2R binds to the annexin A2-S100A10 complex in human podocytes

Abstract Phospholipase A2 receptor (PLA2R) is a member of the mannose receptor family found in podocytes in human kidney. PLA2R is the target of the autoimmune disease, membranous nephropathy, characterised by production of anti-PLA2R autoantibodies which bind to the podocyte. However the function o...

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Autores principales:	Maryline Fresquet, Thomas A. Jowitt, Edward A. McKenzie, Matthew D. Ball, Michael J. Randles, Rachel Lennon, Paul E. Brenchley
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/2153c86a3e0c4f218eab15f2eb4b83f0
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spelling	oai:doaj.org-article:2153c86a3e0c4f218eab15f2eb4b83f02021-12-02T11:41:10ZPLA2R binds to the annexin A2-S100A10 complex in human podocytes10.1038/s41598-017-07028-82045-2322https://doaj.org/article/2153c86a3e0c4f218eab15f2eb4b83f02017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-07028-8https://doaj.org/toc/2045-2322Abstract Phospholipase A2 receptor (PLA2R) is a member of the mannose receptor family found in podocytes in human kidney. PLA2R is the target of the autoimmune disease, membranous nephropathy, characterised by production of anti-PLA2R autoantibodies which bind to the podocyte. However the function of PLA2R in health and in disease remains unclear. To gain insight into the molecular mechanisms of PLA2R function, we searched for its endogenous binding partners. Proteomic analysis identified annexinA2 as a potential interactor with the extracellular domains of PLA2R. We confirmed that PLA2R binds to annexinA2-S100A10 (A2t) complex with specific high affinity to the S100A10 component. The binding occured within the PLA2R NC3 fragment and was increased in acidic pH. Furthermore Ca2+ promoted the association of the PLA2R-A2t complex with phospholipid membranes in vitro. Within the podocyte, all three proteins were enriched in the plasma membrane and organelle membrane compartments. PLA2R co-localised with S100A10 at the cell surface and in extracellular vesicles. This novel interaction between PLA2R and the A2t complex offers insights into the role of PLA2R in podocytes and how autoantibodies might disrupt PLA2R function. The ability of podocytes to secrete vesicles containing PLA2R provides a route for engagement of PLA2R with the immune system.Maryline FresquetThomas A. JowittEdward A. McKenzieMatthew D. BallMichael J. RandlesRachel LennonPaul E. BrenchleyNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Maryline Fresquet Thomas A. Jowitt Edward A. McKenzie Matthew D. Ball Michael J. Randles Rachel Lennon Paul E. Brenchley PLA2R binds to the annexin A2-S100A10 complex in human podocytes
description	Abstract Phospholipase A2 receptor (PLA2R) is a member of the mannose receptor family found in podocytes in human kidney. PLA2R is the target of the autoimmune disease, membranous nephropathy, characterised by production of anti-PLA2R autoantibodies which bind to the podocyte. However the function of PLA2R in health and in disease remains unclear. To gain insight into the molecular mechanisms of PLA2R function, we searched for its endogenous binding partners. Proteomic analysis identified annexinA2 as a potential interactor with the extracellular domains of PLA2R. We confirmed that PLA2R binds to annexinA2-S100A10 (A2t) complex with specific high affinity to the S100A10 component. The binding occured within the PLA2R NC3 fragment and was increased in acidic pH. Furthermore Ca2+ promoted the association of the PLA2R-A2t complex with phospholipid membranes in vitro. Within the podocyte, all three proteins were enriched in the plasma membrane and organelle membrane compartments. PLA2R co-localised with S100A10 at the cell surface and in extracellular vesicles. This novel interaction between PLA2R and the A2t complex offers insights into the role of PLA2R in podocytes and how autoantibodies might disrupt PLA2R function. The ability of podocytes to secrete vesicles containing PLA2R provides a route for engagement of PLA2R with the immune system.
format	article
author	Maryline Fresquet Thomas A. Jowitt Edward A. McKenzie Matthew D. Ball Michael J. Randles Rachel Lennon Paul E. Brenchley
author_facet	Maryline Fresquet Thomas A. Jowitt Edward A. McKenzie Matthew D. Ball Michael J. Randles Rachel Lennon Paul E. Brenchley
author_sort	Maryline Fresquet
title	PLA2R binds to the annexin A2-S100A10 complex in human podocytes
title_short	PLA2R binds to the annexin A2-S100A10 complex in human podocytes
title_full	PLA2R binds to the annexin A2-S100A10 complex in human podocytes
title_fullStr	PLA2R binds to the annexin A2-S100A10 complex in human podocytes
title_full_unstemmed	PLA2R binds to the annexin A2-S100A10 complex in human podocytes
title_sort	pla2r binds to the annexin a2-s100a10 complex in human podocytes
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/2153c86a3e0c4f218eab15f2eb4b83f0
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PLA2R binds to the annexin A2-S100A10 complex in human podocytes

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