Document Detail

Renal cells activate the platelet receptor CLEC-2 through podoplanin.
MedLine Citation:
PMID:  18215137     Owner:  NLM     Status:  MEDLINE    
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 microM. The present study identifies podoplanin as a ligand for CLEC-2 on renal cells.
Charita 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
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Biochemical journal     Volume:  411     ISSN:  1470-8728     ISO Abbreviation:  Biochem. J.     Publication Date:  2008 Apr 
Date Detail:
Created Date:  2008-03-12     Completed Date:  2008-04-15     Revised Date:  2014-02-19    
Medline Journal Info:
Nlm Unique ID:  2984726R     Medline TA:  Biochem J     Country:  England    
Other Details:
Languages:  eng     Pagination:  133-40     Citation Subset:  IM    
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MeSH Terms
Cell Line
Cloning, Molecular
Kidney / chemistry,  cytology*
Lectins, C-Type / metabolism*
Membrane Glycoproteins / analysis,  metabolism*
Podocytes / chemistry
Protein Binding
Surface Plasmon Resonance
Grant Support
G0801186//Medical Research Council; G116/165//Medical Research Council; G116/165(64081)//Medical Research Council; MC_U137884182//Medical Research Council; PG/07/064/23293//British Heart Foundation; PG/11/4/28645//British Heart Foundation; //Wellcome Trust
Reg. No./Substance:
0/CLEC2B protein, human; 0/Lectins, C-Type; 0/Ligands; 0/Membrane Glycoproteins; 0/PDPN protein, human

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