WASP plays a novel role in regulating platelet responses dependent on alphaIIbbeta3 integrin outside-in signalling

Shcherbina, Anna; Cooley, Jessica; Lutskiy, Maxim I; Benarafa, Charaf; Gilbert, Gary E; Remold-O'Donnell, Eileen (2010). WASP plays a novel role in regulating platelet responses dependent on alphaIIbbeta3 integrin outside-in signalling. British journal of haematology, 148(3), pp. 416-27. Oxford: Wiley-Blackwell 10.1111/j.1365-2141.2009.07959.x

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The most consistent feature of Wiskott Aldrich syndrome (WAS) is profound thrombocytopenia with small platelets. The responsible gene encodes WAS protein (WASP), which functions in leucocytes as an actin filament nucleating agent -yet- actin filament nucleation proceeds normally in patient platelets regarding shape change, filopodia and lamellipodia generation. Because WASP localizes in the platelet membrane skeleton and is mobilized by alphaIIbbeta3 integrin outside-in signalling, we questioned whether its function might be linked to integrin. Agonist-induced alphaIIbbeta3 activation (PAC-1 binding) was normal for patient platelets, indicating normal integrin inside-out signalling. Inside-out signalling (fibrinogen, JON/A binding) was also normal for wasp-deficient murine platelets. However, adherence/spreading on immobilized fibrinogen was decreased for patient platelets and wasp-deficient murine platelets, indicating decreased integrin outside-in responses. Another integrin outside-in dependent response, fibrin clot retraction, involving contraction of the post-aggregation actin cytoskeleton, was also decreased for patient platelets and wasp-deficient murine platelets. Rebleeding from tail cuts was more frequent for wasp-deficient mice, suggesting decreased stabilisation of the primary platelet plug. In contrast, phosphatidylserine exposure, a pro-coagulant response, was enhanced for WASP-deficient patient and murine platelets. The collective results reveal a novel function for WASP in regulating pro-aggregatory and pro-coagulant responses downstream of integrin outside-in signalling.

Item Type:	Journal Article (Original Article)
Division/Institute:	04 Faculty of Medicine > Pre-clinic Human Medicine > Theodor Kocher Institute
UniBE Contributor:	Benarafa, Charaf
ISSN:	0007-1048
Publisher:	Wiley-Blackwell
Language:	English
Submitter:	Factscience Import
Date Deposited:	04 Oct 2013 14:07
Last Modified:	05 Dec 2022 14:00
Publisher DOI:	10.1111/j.1365-2141.2009.07959.x
PubMed ID:	19863535
Web of Science ID:	000273547000008
URI:	https://boris.unibe.ch/id/eprint/245 (FactScience: 197088)