The organizing principle of the platelet glycoprotein Ib–IX–V complex

Li, Renhao; Emsley, Jonas

doi:10.1111/jth.12144

Cited by 138 publications

(137 citation statements)

References 107 publications

(138 reference statements)

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“…12,14 Of note, platelet-leukocyte aggregate formation has been identified as a more sensitive marker of platelet activation than P-selectin. 47,48 Several potential counter-receptors exist on leukocytes for platelet GPIbα, 49 and their differential role in arteriogenesis should be addressed in future studies. However, Mac-1 has previously been shown to be critical in this process.…”

Section: Discussionmentioning

confidence: 99%

Critical Role of Platelet Glycoprotein Ibα in Arterial Remodeling

Chandraratne¹,

Bruehl²,

Pagel³

et al. 2015

ATVB

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Objective— Arteriogenesis is strongly dependent on the recruitment of leukocytes, especially monocytes, into the perivascular space of growing collateral vessels. On the basis of previous findings that platelets are central players in inflammatory processes and mediate the recruitment of leukocytes, the aim of this study was to assess the role of platelets in a model of arterial remodeling. Approach and Results— C57Bl6 wild-type mice, IL4-R/Iba mice lacking the extracellular domain of the glycoprotein Ibα (GPIbα) receptor, and mice treated with antibodies to block GPIbα or deplete circulating platelets were studied in peripheral arteriogenesis. Using a novel model of intravital 2-photon and epifluorescence imaging, we visualized and quantified the interaction of platelets with leukocytes and the vascular endothelium in vivo. We found that transient platelet adhesion to the endothelium of collateral vessels was a major event during arteriogenesis and depended on GPIbα. Furthermore, leukocyte recruitment was obviously affected in animals with defective platelet GPIbα function. In IL4-R/Iba mice, transient and firm leukocyte adhesion to the endothelium of collateral vessels, as well as leukocyte accumulation in the perivascular space, were significantly reduced. Furthermore, we detected platelet–leukocyte aggregates within the circulation, which were significantly reduced in IL4-R/Iba animals. Finally, platelet depletion and loss of GPIbα function resulted in poor reperfusion recovery as determined by laser Doppler imaging. Conclusions— Thus, GPIbα-mediated interactions between platelets and endothelial cells, as well as leukocytes, support innate immune cell recruitment and promote arteriogenesis-establishing platelets as critical players in this process.

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Section: Discussionmentioning

confidence: 99%

Critical Role of Platelet Glycoprotein Ibα in Arterial Remodeling

Chandraratne¹,

Bruehl²,

Pagel³

et al. 2015

ATVB

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“…15 Crystal structures of the GPIba N-terminal domain in complex with VWF-A1 have been determined. 16,17 Its association with VWF-A1 is classified as a catch-bond 18,19 or flex-bond, 20 which better facilitates the tethering of platelets to VWF under flow.…”

Section: Introductionmentioning

confidence: 99%

Identification of a juxtamembrane mechanosensitive domain in the platelet mechanosensor glycoprotein Ib-IX complex

Zhang

Deng

Zhou

et al. 2015

Blood

160

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“…GPVI is known as a primary collagen receptor, while the GP Ib-IX-V complex binds to the von Willebrand factor and diverse ligands including coagulation factor XI (FXI), factor XII, thrombin, and P-selectin (3,4). The existence of various ligands of the GP Ib-IX-V complex indicates that this receptor complex governs platelet function via multiple signaling pathways (5).…”

mentioning

confidence: 99%

Molecular basis for unique specificity of human TRAF4 for platelets GPIbβ and GPVI

Kim

Son

Kim

et al. 2017

Proc. Natl. Acad. Sci. U.S.A.

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Tumor necrosis factor (TNF)-receptor associated factor 4 (TRAF4), an adaptor protein with E3-ligase activity, is involved in embryogenesis, cancer initiation and progression, and platelet receptor (GPIb-IX-V complex and GPVI)-mediated signaling for reactive oxygen species (ROS) production that initiates thrombosis at arterial shears. Disruption of platelet receptors and the TRAF4 interaction is a potential target for therapeutic intervention by antithrombotic drugs. Here, we report a crystal structure of TRAF4 (amino acid residues 290∼470) in complex with a peptide from the GPIbβ receptor (amino acid residues 177∼181). The GPIbβ peptide binds to a unique shallow surface composed of two hydrophobic pockets on TRAF4. Further studies revealed the TRAF4-binding motif Arg-Leu-X-Ala. The TRAF4-binding motif was present not only in platelet receptors but also in the TGF-β receptor. The current structure will provide a template for furthering our understanding of the receptor-binding specificity of TRAF4, TRAF4-mediated signaling, and related diseases.T he glycoprotein (GP) Ib-IX-V complex and GPVI are two major platelet receptors that mediate the initial adhesion of platelets to the injured vascular wall for initiating thrombus formation, and they are involved in thrombotic diseases such as stroke and myocardial infarction (1, 2). GPVI is known as a primary collagen receptor, while the GP Ib-IX-V complex binds to the von Willebrand factor and diverse ligands including coagulation factor XI (FXI), factor XII, thrombin, and P-selectin (3, 4). The existence of various ligands of the GP Ib-IX-V complex indicates that this receptor complex governs platelet function via multiple signaling pathways (5). The GP Ib-IX-V complex, consisting of GPIbα (the major ligand-binding subunit), GPIbβ, GPIX, and GPV, is the second most abundant receptor in platelets and is physically and functionally linked to another platelet receptor, GPVI (3).Tumor necrosis factor (TNF)-receptor associated factor 4 (TRAF4) is one of the seven identified TRAF1∼TRAF7 factors in mammals and was initially identified as a regulator of embryogenesis in mice, especially in the central and peripheral nervous system (6). TRAF4 is involved in gross tracheal, neural tube, and skeletal formation (7-9). The involvement of TRAF4 in the initiation and progression of many types of cancer has also been reported, suggesting that TRAF4 is a tentative therapeutic target for cancer treatment (10, 11). Unlike other TRAF family members, TRAF4 contains a nuclear localization signal (NLS) and does not interact with canonical TRAF-binding receptors such as TNFR2, CD30, and CD40, indicating that TRAF4 is not involved in cellular signaling that is mediated by the typical TRAF family (12, 13).Because of the critical function of the TRAF family in various signaling events, including immunity, inflammation, and apoptosis, these have been the main focus of functional, structural, and biochemical analyses of these proteins (13). Intensive study has revealed that the TRAF family, except...

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The organizing principle of the platelet glycoprotein Ib–IX–V complex

Cited by 138 publications

References 107 publications

Critical Role of Platelet Glycoprotein Ibα in Arterial Remodeling

Critical Role of Platelet Glycoprotein Ibα in Arterial Remodeling

Identification of a juxtamembrane mechanosensitive domain in the platelet mechanosensor glycoprotein Ib-IX complex

Molecular basis for unique specificity of human TRAF4 for platelets GPIbβ and GPVI

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