Renal cells activate the platelet receptor CLEC-2 through podoplanin

Charta M. Christou, Andrew C. Pearce, Aleksandra A. Watson, Anita R. Mistry, Alice Y. Pollitt, Angharad E. Fenton-May, Louise A. Johnson, David G. Jackson, Steve P. Watson, Chris A. O'Callaghan

Research output: Contribution to journalArticlepeer-review

Abstract

We have recently shown that the C-type lectin-like receptor, CLEC-2, is expressed on platelets and that it mediates powerful platelet aggregation by the snake venom toxin rhodocytin. In addition, we have provided indirect evidence for an endogenous ligand for CLEC-2 in renal cells expressing HIV-1. This putative ligand facilitates transmission of HIV through its incorporation into the viral envelope and binding to CLEC-2 on platelets. The aim of the present study was to identify the ligand on these cells which binds to CLEC-2 on platelets. Recombinant CLEC-2 exhibits specific binding to HEK-293T (human embryonic kidney) cells in which the HIV can be grown. Furthermore, HEK-293T cells activate both platelets and CLEC-2-transfected DT-40 B-cells. The transmembrane protein podoplanin was identified on HEK-293T cells and was demonstrated to mediate both binding of HEK-293T cells to CLEC-2 and HEK-293T cell activation of CLEC-2-transfected DT-40 B-cells. Podoplanin is expressed on renal cells (podocytes). Furthermore, a direct interaction between CLEC-2 and podoplanin was confirmed using surface plasmon resonance and was shown to be independent of glycosylation of CLEC-2. The interaction has an affinity of 24.5 ± 3.7 μM. The present study identifies podoplanin as a ligand for CLEC-2 on renal cells.

Original languageEnglish
Pages (from-to)133-140
Number of pages8
JournalBiochemical Journal
Volume411
Issue number1
DOIs
Publication statusPublished - 1 Apr 2008

Keywords

  • C-type lectin-like receptor 2 (CLEC-2)
  • HIV
  • Platelet
  • Podoplanin
  • Renal cell

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