Abstract Number: PB1023
Meeting: ISTH 2021 Congress
Background: Platelet activity is regulated by a myriad of biochemical signalling pathways which are closely intertwined in function and outcome. We have previously shown canonical WNT signalling effectors in platelets, however, WNT/planar cell polarity (PCP) signalling has not yet been attributed to platelets. WNT/PCP regulates cell polarity and cell movement during key developmental processes such as gastrulation and neural tube closure, through the upstream regulation of small GTPases including RhoA, Rac1 and Cdc42 (Fig. 1).
Aims: To investigate the expression, localisation, and interaction of key WNT/PCP membrane receptors Cadherin EGF LAG Seven-pass G-type Receptor (CELSR), Frizzled (FZD), and Van Gogh-Like (Vangl), in both resting and activated platelets.
Methods: Blood was collected from healthy donors who gave consent under the Declaration of Helsinki. SDS-PAGE/Western blotting, immuno-fluorescence confocal microscopy, immuno-gold labelling electron microscopy, and co-immunoprecipitation were utilised to investigate core WNT/PCP membrane receptors in platelets under resting and varied stages of activation.
Results: We demonstrate that the three key WNT/PCP membrane receptors CELSR, FZD and Vangl, and their downstream signalling effectors, are expressed in both human and murine platelets. In resting platelets, CELSR and Vangl were found to co-localise and co-immunoprecipitate, analogous to WNT/PCP processes regulating cell polarity during morphogenesis. Platelet activation revealed a strong association of Vangl with platelet alpha-granules, translocation of CELSR to the platelet membrane and subsequent release of CELSR on platelet microparticles.
Conclusions: WNT/PCP coordination of morphogenesis is well documented and the discovery of WNT/PCP membrane effectors in platelets adds another layer of complexity to the understanding of platelet signalling processes during activation. The physiologic/pathologic implications of the discovery of these important cell polarity pathway membrane receptors in platelets remains to be fully elucidated.
To cite this abstract in AMA style:P Comer S, Alkazemi N, Hamilton D, O'Neill T, Maguire P. Discovery of WNT/Planar Cell Polarity Membrane Receptors in Platelets [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 1). https://abstracts.isth.org/abstract/discovery-of-wnt-planar-cell-polarity-membrane-receptors-in-platelets/. Accessed September 24, 2021.
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