Journal Article

PLA 2 R binds to the annexin A2-S100A10 complex in human podocytes

Ball, Matthew D, Jowitt, Thomas A, McKenzie, Edward A, Lennon, Rachel, Randles, Michael J, Fresquet, Maryline, Brenchley, Paul E

2017

Overview

Phospholipase A receptor (PLA R) is a member of the mannose receptor family found in podocytes in human kidney. PLA R is the target of the autoimmune disease, membranous nephropathy, characterised by production of anti-PLA R autoantibodies which bind to the podocyte. However the function of PLA R in health and in disease remains unclear. To gain insight into the molecular mechanisms of PLA R function, we searched for its endogenous binding partners. Proteomic analysis identified annexinA2 as a potential interactor with the extracellular domains of PLA R. We confirmed that PLA R binds to annexinA2-S100A10 (A2t) complex with specific high affinity to the S100A10 component. The binding occured within the PLA R NC3 fragment and was increased in acidic pH. Furthermore Ca promoted the association of the PLA R-A2t complex with phospholipid membranes in vitro. Within the podocyte, all three proteins were enriched in the plasma membrane and organelle membrane compartments. PLA R co-localised with S100A10 at the cell surface and in extracellular vesicles. This novel interaction between PLA R and the A2t complex offers insights into the role of PLA R in podocytes and how autoantibodies might disrupt PLA R function. The ability of podocytes to secrete vesicles containing PLA R provides a route for engagement of PLA R with the immune system.

• Subject: Annexin A2 - metabolism / Calcium - metabolism / Cell Line / Cell Membrane - metabolism / Extracellular Vesicles - metabolism / Humans / Podocytes - metabolism / Protein Binding / Receptors, Phospholipase A2 - metabolism / S100 Proteins - metabolism