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J. Biol. Chem., Vol. 277, Issue 4, 3011-3019, January 25, 2002
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From the Department of Medicine, University of Pennsylvania,
Philadelphia, Pennsylvania 19104
The platelet response to collagen is a primary
event in hemostasis and thrombosis, but the precise roles of the
numerous identified platelet collagen receptors remain incompletely
defined. Attention has recently focused on glycoprotein VI (GPVI), a
receptor that is expressed on platelets in association with a signaling
adapter, the Fc receptor gamma chain (Fc R
The Platelet Receptor GPVI Mediates Both Adhesion and Signaling
Responses to Collagen in a Receptor Density-dependent
Fashion*
). Genetic and
pharmacologic loss of GPVI function results in loss of collagen
signaling in platelets, but studies to date have failed to demonstrate
that GPVI-Fc R expression is sufficient to confer collagen signaling responses. These results have led to the hypothesis that collagen responses mediated by GPVI-Fc R may require the collagen-binding integrin 
2
1 as a co-receptor, but this model has not been
supported by a recent study of mouse platelets lacking 21. In the
present study we have used a novel anti-GPVI monoclonal antibody to
measure the level of GPVI on human platelets and to guide the
development of GPVI-expressing cell lines to assess the role of GPVI in
mediating platelet collagen responses. GPVI receptor density on human
platelets appears tightly regulated, is independent from the level of
21 expression, and significantly exceeds that on previously
characterized GPVI-expressing RBL-2H3 cells. Using newly
generated GPVI-expressing RBL-2H3 cells with receptor densities
equivalent to that on human platelets, we demonstrate that GPVI
expression confers both adhesive and signaling responses to collagen in
a graded fashion that is proportional to the GPVI receptor density.
These results resolve some of the conflicting data regarding
GPVI-collagen interactions and demonstrate that 1) GPVI-Fc R
expression is sufficient to confer both adhesion and signaling
responses to collagen, and 2) GPVI-mediated collagen responses are
receptor density-dependent at the receptor levels expressed
on human platelets.
*
This work was supported by grants from the W. W. Smith
Charitable Trust and the American Heart Association (to M. L. K.).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed: University of
Pennsylvania, 421 Curie Blvd., BRB II/III Room 952, Philadelphia, PA
19104-6100. Tel.: 215-898-9007; Fax: 215-573-2094; E-mail: markkahn@mail.med.upenn.edu.
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