The Transmembrane Domains of β and IX Subunits Mediate the Localization of the Platelet Glycoprotein Ib-IX Complex to the Glycosphingolipid-enriched Membrane Domain

Xu, Guofeng; Shang, Dan; Zhang, Zuping; Shaw, Tanner S.; Ran, Yali; López, José A.; Peng, Yuandong

doi:10.1074/jbc.m115.668145

Cited by 3 publications

(2 citation statements)

References 38 publications

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“…On the other hand, we did notice that the difference between these two mice in their shear-induced vWf binding can only be revealed at a shear rate of 15,000s −1 , a condition that is generally not seen in vivo , suggesting that the major impact upon α/β disulfide linkage deficiency was on the GP Ib-IX-vWf binding induced α IIb β 3 activation. Further investigations are needed in order to identify the structural necessity of the β/IX complex to achieve a better inhibition or even an elimination of the GP Ib-IX-GEMs association where both the shear-induced binding function and the vWf-binding induced signaling function of the GP Ib-IX complex could be simultaneously abolished in vivo (7,41). …”

Section: Discussionmentioning

confidence: 99%

Defective Association of the Platelet Glycoprotein Ib–IX Complex with the Glycosphingolipid-Enriched Membrane Domain Inhibits Murine Thrombus and Atheroma Formation

Zhou

Ran

et al. 2016

The Journal of Immunology

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Localization of the platelet glycoprotein Ib-IX complex to the membrane lipid domain is essential for platelet adhesion to von Willebrand factor (vWf) and subsequent platelet activation in vitro. Yet, the in vivo importance of this localization has never been addressed. We recently found that the disulfide linkage between Ibα and Ibβ is critical for the association of Ibα with the glycosphingolipid-enriched membrane (GEM) domain, in this study, we established a transgenic mouse model expressing this mutant human Ibα that is also devoid of endogenous Ibα (HαSSMα−/−). Characterization of this model demonstrated a similar dissociation of Ibα from murine platelet GEMs to that expressed in CHO cells, which correlates well with the impaired adhesion of the transgenic platelets to vWf ex vivo and in vivo. Furthermore, we bred our transgenic mice into an atherosclerosis-prone background (HαSSMα−/−ApoE−/− and HαWTMα−/−ApoE−/−). We observed that atheroma formation was significantly inhibited in mutant mice where fewer platelet-bound CD11c+ leukocytes were circulating (CD45+/CD11c+/CD41+) and residing in atherosclerotic lesions (CD45+/CD11c+), suggesting that platelet-mediated adhesion and infiltration of CD11c+ leukocytes may be one of the mechanisms. These observations provide the first in vivo evidence showing that the membrane GEMs is physiologically and pathophysiologically critical in the function of the GP Ib-IX complex.

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Section: Discussionmentioning

confidence: 99%

Defective Association of the Platelet Glycoprotein Ib–IX Complex with the Glycosphingolipid-Enriched Membrane Domain Inhibits Murine Thrombus and Atheroma Formation

Zhou

Ran

et al. 2016

The Journal of Immunology

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“…The specialized glycosphingolipid‐enriched membranes (GEMs) can regulate the GP Ib‐IX function . In resting platelets, the GEMs uniformly distributes across the plasma membrane .…”

Section: Introductionmentioning

confidence: 99%

Membrane skeleton orchestrates the platelet glycoprotein (GP) Ib‐IX complex clustering and signaling

et al. 2016

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SummaryPlatelet glycoprotein Ib‐IX complex is affixed to the membrane skeleton through interaction with actin binding protein 280 (ABP‐280). We find that removal of the ABP‐280 binding sites in GP Ibα cytoplasmic tail has little impact on the complex clustering induced by antibody crosslinking. However, large truncation of the GP Ibα cytoplasmic tail allows the formation of larger patches of the complex, suggesting that an ABP‐280 independent force may exist. Besides, we observe that the signaling upon GP Ib‐IX clustering is elicited in both membrane lipid domain dependent and independent manner, a choice that relies on how the membrane skeleton interacts with the complex. Our findings suggest a more complex mechanism for how the membrane skeleton regulates the GP Ib‐IX function. © 2016 The Authors IUBMB Life published by Wiley Periodicals, Inc. on behalf of International Union of Biochemistry and Molecular Biology, 68(10):823–829, 2016

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The Platelet Glycoprotein Ib-IX-V Complex

López

2017

Platelets in Thrombotic and Non-Thrombotic Disorders

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The Transmembrane Domains of β and IX Subunits Mediate the Localization of the Platelet Glycoprotein Ib-IX Complex to the Glycosphingolipid-enriched Membrane Domain

Cited by 3 publications

References 38 publications

Defective Association of the Platelet Glycoprotein Ib–IX Complex with the Glycosphingolipid-Enriched Membrane Domain Inhibits Murine Thrombus and Atheroma Formation

Defective Association of the Platelet Glycoprotein Ib–IX Complex with the Glycosphingolipid-Enriched Membrane Domain Inhibits Murine Thrombus and Atheroma Formation

Membrane skeleton orchestrates the platelet glycoprotein (GP) Ib‐IX complex clustering and signaling

The Platelet Glycoprotein Ib-IX-V Complex

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