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

doi:10.1042/BJ20071216

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

School of Life and Health Sciences

Research output: Contribution to journal › Article › peer-review

79 Citations (Scopus)

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 language	English
Pages (from-to)	133-140
Number of pages	8
Journal	Biochemical Journal
Volume	411
Issue number	1
DOIs	https://doi.org/10.1042/BJ20071216
Publication status	Published - 1 Apr 2008

Keywords

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

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10.1042/BJ20071216

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title = "Renal cells activate the platelet receptor CLEC-2 through podoplanin",

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.",

keywords = "C-type lectin-like receptor 2 (CLEC-2), HIV, Platelet, Podoplanin, Renal cell",

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

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AU - Christou, Charta M.

AU - Pearce, Andrew C.

AU - Watson, Aleksandra A.

AU - Mistry, Anita R.

AU - Pollitt, Alice Y.

AU - Fenton-May, Angharad E.

AU - Johnson, Louise A.

AU - Jackson, David G.

AU - Watson, Steve P.

AU - O'Callaghan, Chris A.

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N2 - 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.

AB - 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.

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KW - Renal cell

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Renal cells activate the platelet receptor CLEC-2 through podoplanin

Abstract

Keywords

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