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Pathophysiological consequences of receptor mistraffic: Tales from the platelet P2Y12 receptor

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Pathophysiological consequences of receptor mistraffic : Tales from the platelet P2Y12 receptor. / Cunningham, Margaret R.; Aungraheeta, Riyaad; Mundell, Stuart J.

In: Molecular and Cellular Endocrinology, Vol. 449, 05.07.2017, p. 74-81.

Research output: Contribution to journalArticle

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Cunningham, MR, Aungraheeta, R & Mundell, SJ 2017, 'Pathophysiological consequences of receptor mistraffic: Tales from the platelet P2Y12 receptor', Molecular and Cellular Endocrinology, vol. 449, pp. 74-81. https://doi.org/10.1016/j.mce.2017.02.016

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Cunningham, Margaret R. ; Aungraheeta, Riyaad ; Mundell, Stuart J. / Pathophysiological consequences of receptor mistraffic : Tales from the platelet P2Y12 receptor. In: Molecular and Cellular Endocrinology. 2017 ; Vol. 449. pp. 74-81.

Bibtex

@article{0680fe068a0a4429af4c600065355157,
title = "Pathophysiological consequences of receptor mistraffic: Tales from the platelet P2Y12 receptor",
abstract = "Genetic variations in G protein-coupled receptor (GPCR) genes can disrupt receptor function in a wide variety of human genetic diseases, including platelet bleeding disorders. Platelets are critical for haemostasis with inappropriate platelet activation leading to the development of arterial thrombosis, which can result in heart attack and stroke whilst decreased platelet activity is associated with an increased risk of bleeding. GPCRs expressed on the surface of platelets play key roles in regulating platelet activity and therefore function. Receptors include purinergic receptors (P2Y1 and P2Y12), proteinase-activated receptor (PAR1 and PAR4) and thromboxane receptors (TPα), among others. Pharmacological blockade of these receptors forms a powerful therapeutic tool in the treatment and prevention of arterial thrombosis. With the advance of genomic technologies, there has been a substantial increase in the identification of naturally occurring rare and common GPCR variants. These variants include single-nucleotide polymorphisms (SNPs) and insertion or deletions that have the potential to alter GPCR expression or function. A number of defects in platelet GPCRs that disrupt receptor function have now been characterized in patients with mild bleeding disorders. This review will focus on rare, function-disrupting variants of platelet GPCRs with particular emphasis upon mutations in the P2Y12 receptor gene that affect receptor traffic to modulate platelet function. Further this review will outline how the identification and characterization of function-disrupting GPCR mutations provides an essential link in translating our detailed understanding of receptor traffic and function in cell line studies into relevant human biological systems.",
author = "Cunningham, {Margaret R.} and Riyaad Aungraheeta and Mundell, {Stuart J.}",
year = "2017",
month = "7",
day = "5",
doi = "10.1016/j.mce.2017.02.016",
language = "English",
volume = "449",
pages = "74--81",
journal = "Molecular and Cellular Endocrinology",
issn = "0303-7207",
publisher = "Elsevier Science Ireland",

}

RIS - suitable for import to EndNote

TY - JOUR

T1 - Pathophysiological consequences of receptor mistraffic

T2 - Tales from the platelet P2Y12 receptor

AU - Cunningham, Margaret R.

AU - Aungraheeta, Riyaad

AU - Mundell, Stuart J.

PY - 2017/7/5

Y1 - 2017/7/5

N2 - Genetic variations in G protein-coupled receptor (GPCR) genes can disrupt receptor function in a wide variety of human genetic diseases, including platelet bleeding disorders. Platelets are critical for haemostasis with inappropriate platelet activation leading to the development of arterial thrombosis, which can result in heart attack and stroke whilst decreased platelet activity is associated with an increased risk of bleeding. GPCRs expressed on the surface of platelets play key roles in regulating platelet activity and therefore function. Receptors include purinergic receptors (P2Y1 and P2Y12), proteinase-activated receptor (PAR1 and PAR4) and thromboxane receptors (TPα), among others. Pharmacological blockade of these receptors forms a powerful therapeutic tool in the treatment and prevention of arterial thrombosis. With the advance of genomic technologies, there has been a substantial increase in the identification of naturally occurring rare and common GPCR variants. These variants include single-nucleotide polymorphisms (SNPs) and insertion or deletions that have the potential to alter GPCR expression or function. A number of defects in platelet GPCRs that disrupt receptor function have now been characterized in patients with mild bleeding disorders. This review will focus on rare, function-disrupting variants of platelet GPCRs with particular emphasis upon mutations in the P2Y12 receptor gene that affect receptor traffic to modulate platelet function. Further this review will outline how the identification and characterization of function-disrupting GPCR mutations provides an essential link in translating our detailed understanding of receptor traffic and function in cell line studies into relevant human biological systems.

AB - Genetic variations in G protein-coupled receptor (GPCR) genes can disrupt receptor function in a wide variety of human genetic diseases, including platelet bleeding disorders. Platelets are critical for haemostasis with inappropriate platelet activation leading to the development of arterial thrombosis, which can result in heart attack and stroke whilst decreased platelet activity is associated with an increased risk of bleeding. GPCRs expressed on the surface of platelets play key roles in regulating platelet activity and therefore function. Receptors include purinergic receptors (P2Y1 and P2Y12), proteinase-activated receptor (PAR1 and PAR4) and thromboxane receptors (TPα), among others. Pharmacological blockade of these receptors forms a powerful therapeutic tool in the treatment and prevention of arterial thrombosis. With the advance of genomic technologies, there has been a substantial increase in the identification of naturally occurring rare and common GPCR variants. These variants include single-nucleotide polymorphisms (SNPs) and insertion or deletions that have the potential to alter GPCR expression or function. A number of defects in platelet GPCRs that disrupt receptor function have now been characterized in patients with mild bleeding disorders. This review will focus on rare, function-disrupting variants of platelet GPCRs with particular emphasis upon mutations in the P2Y12 receptor gene that affect receptor traffic to modulate platelet function. Further this review will outline how the identification and characterization of function-disrupting GPCR mutations provides an essential link in translating our detailed understanding of receptor traffic and function in cell line studies into relevant human biological systems.

U2 - 10.1016/j.mce.2017.02.016

DO - 10.1016/j.mce.2017.02.016

M3 - Article

C2 - 28212842

VL - 449

SP - 74

EP - 81

JO - Molecular and Cellular Endocrinology

JF - Molecular and Cellular Endocrinology

SN - 0303-7207

ER -