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The WASH-complex subunit Strumpellin regulates integrin αIIbβ3 trafficking in murine platelets

1University Hospital Würzburg and Rudolf Virchow Center for Integrative and Translational Bioimaging, University of Würzburg, Würzburg, Bayern, Germany, 2Institute of Experimental Biomedicine, University Hospital Würzburg and Rudolf Virchow Center for Integrative and Translational Bioimaging, University of Würzburg, Würzburg, Bayern, Germany, 3Cancer Research UK Beatson Institute, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, Scotland, United Kingdom

Abstract Number: PB0386

Meeting: ISTH 2022 Congress

Theme: Platelets and Megakaryocytes » Platelet Receptors

Background: The platelet specific integrin αIIbβ3 mediates platelet adhesion, aggregation and plays a central role in thrombosis and hemostasis. In resting platelets, αIIbβ3 is expressed on the membrane surface and in intracellular compartments. Upon platelet activation, the number of surface-expressed αIIbβ3 is increased by the translocation of internal granule pools to the plasma membrane. The five-subunit Wiskott-Aldrich syndrome protein and Scar homologue (WASH) complex is the major endosomal actin polymerization-promoting complex and has been implicated in the generation of actin networks involved in endocytic trafficking of integrins in other cell types. Strumpellin is a subunit of the WASH complex but its role in platelet function is unknown.

Aims: The aim of this study was to investigate the role of Strumpellin in platelet function.

Methods: We took advantage of the megakaryocyte/platelet-specific Strumpellin-deficient mice and performed flow cytometry, qPCR, quantitative mass spectrometry and different microscopic techniques.

Results: Strumpellin-deficient mice displayed a normal platelet count. In contrast to other surface membrane glycoproteins (e.g. α2, β1, GPV, GPIb) the surface expression of integrin αIIbβ3 was approximately 20% decreased on Strumpellin-deficient platelets. While the release of the internal αIIbβ3 pool after platelet activation was unaffected, fibrinogen uptake was delayed. The number of platelet α-granules was slightly but significantly increased in Strumpellin-deficient platelets. Interestingly, reduced integrin αIIbβ3 expression was also observed in primary Strumpellin-deficient megakaryocytes, however their ploidy levels were unaltered. Quantitative PCR revealed normal mRNA level of Itga2b and Itgb3 in mutant megakaryocytes, suggesting unaltered transcription of these genes. Quantitative proteome analysis of isolated αIIbβ3-positive vesicular structures from Strumpellin-deficient platelets revealed an enrichment of protein markers, which are associated with the endoplasmatic reticulum, Golgi complex and early endosomes.

Conclusion(s): These results point to a so far unidentified role of the WASH complex subunit Strumpellin in integrin αIIbβ3 trafficking in murine platelets.

To cite this abstract in AMA style:

Spindler M, Schurr Y, Reil L, Nieswandt B, Machesky L, Bender M. The WASH-complex subunit Strumpellin regulates integrin αIIbβ3 trafficking in murine platelets [abstract]. https://abstracts.isth.org/abstract/the-wash-complex-subunit-strumpellin-regulates-integrin-%ce%b1iib%ce%b23-trafficking-in-murine-platelets/. Accessed October 1, 2023.

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