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Platelet Adhesion to exposed collagen
Stable Identifier
R-HSA-75892
DOI
10.3180/R-HSA-75892.6
Type
Pathway
Species
Homo sapiens
ReviewStatus
5/5
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Hemostasis (Homo sapiens)
Platelet Adhesion to exposed collagen (Homo sapiens)
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Initiation of platelet adhesion is the first step in the formation of the platelet plug. Circulating platelets are arrested and subsequently activated by exposed collagen and von Willebrand factor (VWF). It is not entirely clear which type of collagen is responsible for adhesion and activation; collagen types I and III are abundant in vascular epithelia but several other types including IV are present (Farndale RW 2006). Several collagen binding proteins are expressed on platelets, including integrin alpha2 beta1 (α2β1 or ITGA2:ITGB1), GPVI, and GPIV. ITGA2:ITGB1, known on leukocytes as VLA-2, is the major platelet collagen receptor (Kunicki TJ et al., 1988). ITGA2:ITGB1 (α2β1) requires Mg2+ to interact with collagen. The activation of ITGA2:ITGB1 (α2β1) is modulated by the activation of integrin alphaIIb beta3 (αIIbβ3 or ITGA2B:ITGB3), which functions as a platelet receptor for fibrinogen and VWF (van de Walle GR et al., 2007). The I domain of α2 (ITGA2) subunit binds a collagen motif with the sequence Gly-Phe-Hyp-Gly-Glu-Arg (Emsley J et al., 2000). Binding of collagen to ITGA2:ITGB1 (α2β1) generates intracellular signals that contribute to platelet activation. These interactions facilitate the engagement of the lower-affinity collagen receptor, GPVI (Tsuji M et al., 1997), the key receptor involved in collagen-induced platelet activation. The GPVI receptor is a complex of the GPVI protein with a dimer of Fc epsilon R1 gamma (FceRI gamma). The Src family kinases Fyn and Lyn constitutively associate with the GPVI:FceRIgamma complex in platelets and initiate platelet activation through phosphorylation of the immunoreceptor tyrosine-based activation motif (ITAM) in FceRI gamma, leading to binding and activation of the tyrosine kinase Syk. Downstream of Syk, a series of adapter molecules and effectors lead to platelet activation. VWF circulates in plasma as a multimeric molecule that senses hydrodynamic shear forces in the bloodstream (Reininger AJ 2008; Mojzisch A & Brehm MA 2021). Upon vascular injury, circulating VWF binds to subendothelial collagen, which becomes exposed to the flowing blood (Bergmeier W & Hynes RO 2012; Colace TV & Diamond SL 2013). Upon binding to collagen, VWF becomes anchored to the damaged surface. Shear forces then induce conformational changes to mechanosensitive VWF causing the bound VWF to stretch and unfold (Li F et al., 2004; Schneider SW et al., 2007; Fu H et al., 2017). VWF unfolding leads to exposure of the A1 domain to allow binding to glycoprotein Ib α (GPIbα, encoded by GP1BA), a subunit of the platelet surface GPIb:IX:V complex (Dumas JJ et al., 2004; Ju L et al., 2013). Shear-induced aggregation is achieved when VWF interacts both with exposed collagen and platelets to initiate platelet adhesion to vascular injury sites. The interaction between VWF and GPIb is regulated by shear force; an increase in the shear stress results in a corresponding increase in the affinity of VWF for GPIb.
Literature References
PubMed ID
Title
Journal
Year
9295288
A novel association of Fc receptor gamma-chain with glycoprotein VI and their co-expression as a collagen receptor in human platelets
Tsuji, M
,
Arai, M
,
Ezumi, Y
,
Takayama, H
J Biol Chem
1997
12356768
Analysis of the interaction of platelet collagen receptor glycoprotein VI (GPVI) with collagen. A dimeric form of GPVI, but not the monomeric form, shows affinity to fibrous collagen
Moroi, M
,
Miura, Y
,
Takahashi, T
,
Jung, SM
J Biol Chem
2002
Participants
Events
Collagen type I binds integrin alpha1beta1, alpha2beta1, alpha10beta1
(Homo sapiens)
Interaction of GPVI and FceRI gamma
(Homo sapiens)
GPVI binds Fyn and Lyn
(Homo sapiens)
Binding of GPVI:Fc Epsilon R1 gamma receptor complex with collagen
(Homo sapiens)
VWF multimer binds to collagen type I
(Homo sapiens)
GPIb:IX:V binds to VWF multimer:collagen
(Homo sapiens)
ADAMTS13 cleaves VWF multimer
(Homo sapiens)
Caplacizumab binds VWF
(Homo sapiens)
Participates
as an event of
Hemostasis (Homo sapiens)
Orthologous Events
Platelet Adhesion to exposed collagen (Bos taurus)
Platelet Adhesion to exposed collagen (Canis familiaris)
Platelet Adhesion to exposed collagen (Danio rerio)
Platelet Adhesion to exposed collagen (Gallus gallus)
Platelet Adhesion to exposed collagen (Mus musculus)
Platelet Adhesion to exposed collagen (Rattus norvegicus)
Platelet Adhesion to exposed collagen (Sus scrofa)
Platelet Adhesion to exposed collagen (Xenopus tropicalis)
Authored
de Bono, B (2004-08-13)
Reviewed
Gao, R (2023-11-09)
Created
Farndale, R (2004-09-25)
Pace, NP (2004-09-25)
de Bono, B (2004-09-25)
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