Journal
JOURNAL OF THROMBOSIS AND HAEMOSTASIS
Volume 7, Issue -, Pages 191-194Publisher
WILEY
DOI: 10.1111/j.1538-7836.2009.03372.x
Keywords
CLEC-2; collagen; GPVI; laminin; platelet; podoplanin
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We have identified a novel platelet membrane protein, CLEC-2 as a receptor for rhodocytin, a platelet-activating snake venom. CLEC-2 is specifically expressed in platelets and megakaryocytes, and has an atypical ITAM, which undergoes tyrosine phosphorylation by Src kinases, resulting in downstream signaling including Syk, SLP-76 and PLC gamma 2. We found that CLEC-2 is the receptor for podoplanin, a sialoglycoprotein implicated in tumor-induced platelet aggregation and tumor metastasis. VWF bridges exposed collagen, at damaged vessels, to GPIb. Subsequently, GPVI binds to collagen, leading to integrin alpha 2 beta 1 activation. We found that platelets adhere to laminin, another major ECM component, through integrin alpha 6 beta 1, and are activated through GPVI. This is the first report on GPVI having a ligand, laminin, other than collagen. Laminin also interacts with VWF, leading to platelet adhesion via GPIb under sheer stress. The redundancy of platelet interactions with laminin and with collagen may serve to promote hemostasis at sites of damaged vessels.
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