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β-arrestin-1 participates in thrombosis and regulates integrin aIIbβ3 signalling without affecting P2Y receptors desensitisation and function.
- Source :
-
Thrombosis and haemostasis [Thromb Haemost] 2012 Apr; Vol. 107 (4), pp. 735-48. Date of Electronic Publication: 2012 Feb 08. - Publication Year :
- 2012
-
Abstract
- β-arrestin-1 (β-arr1) and β-arrestin-2 (β-arr2) are cytosolic proteins well-known to participate in G protein-coupled receptor desensitisation and signalling. We used genetically-inactivated mice to evaluate the role of β-arr1 or β-arr2 in platelet function, P2Y receptor desensitisation, haemostasis and thrombosis. Platelet aggregation, soluble fibrinogen binding and P-selectin exposure induced by various agonists were near normal in β-arr1-/- and β-arr2-/- platelets. In addition, deficiency in β-arr1 or β-arr2 was not critical for P2Y receptors desensitisation. A functional redundancy between β-arr1 and β-arr2 may explain these unchanged platelet responses. Interestingly, β-arr1-/- but not β-arr2-/- mice were protected against laser- and FeCl3-induced thrombosis. The tail bleeding times, number of rebleeds and volume of blood loss were unchanged in β-arr1-/- and β-arr2-/- mice, suggesting no defect in haemostasis. β-arr1-/- platelet activation upon adhesion to immobilised fibrinogen was inhibited, as attested by a 37 ± 5% (n = 3, p<0.0001) decrease in filopodia extension, suggesting defective signalling through integrin αIIbβ3. β-arr1 appeared to be located downstream of Src family kinases and to regulate αIIbβ3 signalling by increasing Akt phosphorylation. Overall, this study supports a role for β-arr1 in promoting thrombus formation, in part through its participation in αIIbβ3 signalling, and no role of β-arr1 and β-arr2 in agonist-induced platelet activation and P2Y receptors desensitisation.
- Subjects :
- Animals
Blood Platelets metabolism
Calcium metabolism
Carotid Arteries pathology
Cell Adhesion
Enzyme-Linked Immunosorbent Assay methods
Fibrinogen metabolism
Hemorrhage
Mesenteric Arteries pathology
Mice
Mice, Transgenic
Microscopy, Electron, Scanning methods
P-Selectin metabolism
Phosphorylation
Signal Transduction
Thrombosis metabolism
beta-Arrestin 1
beta-Arrestin 2
beta-Arrestins
Arrestins biosynthesis
Platelet Glycoprotein GPIIb-IIIa Complex metabolism
Receptors, Purinergic P2Y metabolism
Thrombosis blood
Subjects
Details
- Language :
- English
- ISSN :
- 2567-689X
- Volume :
- 107
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Thrombosis and haemostasis
- Publication Type :
- Academic Journal
- Accession number :
- 22318609
- Full Text :
- https://doi.org/10.1160/TH11-06-0430