PLA 2 R Binds to the Annexin A2-S100A10 Complex in Human Podocytes

Sci Rep. 2017 Jul 31;7(1):6876. doi: 10.1038/s41598-017-07028-8.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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*

Substances

  • Annexin A2
  • Receptors, Phospholipase A2
  • S100 Proteins
  • S100 calcium binding protein A10
  • Calcium