BACKGROUND: The A subunit of factor XIII (FXIII-A) functions as an intracellular transglutaminase (TG) in the megakaryocyte/platelet lineage, where it probably participates in the cytoskeletal remodeling associated with cell activation. However, so far, the precise role of cellular FXIII (cFXIII) and the functional consequences of its absence in FXIII-A-deficient patients are unknown. OBJECTIVES AND METHODS: In this study, we used platelets from four patients with congenital deficiency of FXIII-A to study the role of cFXIII in platelet functions. RESULTS: We found that FXIII-A represents the only detectable source of TG activity in platelets and that the binding of fibrinogen in response to thrombin receptor agonist peptide (TRAP) stimulation was significantly reduced in platelets from the patients. In agreement with this, in control platelets, monodansyl-cadaverine (MDC), a competitive amino-donor for TGs, inhibited fibrinogen binding induced by TRAP in a dose-dependent manner. Moreover, upon adhesion to fibrinogen, normal platelets incubated with MDC as well as FXIII-A-deficient platelets showed a distinct extension pattern with reduced lamellipodia and increased filopodia formation, suggesting a delay in spreading. CONCLUSIONS: These findings provide evidence for the direct involvement of cFXIII-dependent TG activity in the regulation of platelet functions.
BACKGROUND: The A subunit of factor XIII (FXIII-A) functions as an intracellular transglutaminase (TG) in the megakaryocyte/platelet lineage, where it probably participates in the cytoskeletal remodeling associated with cell activation. However, so far, the precise role of cellular FXIII (cFXIII) and the functional consequences of its absence in FXIII-A-deficient patients are unknown. OBJECTIVES AND METHODS: In this study, we used platelets from four patients with congenital deficiency of FXIII-A to study the role of cFXIII in platelet functions. RESULTS: We found that FXIII-A represents the only detectable source of TG activity in platelets and that the binding of fibrinogen in response to thrombin receptor agonist peptide (TRAP) stimulation was significantly reduced in platelets from the patients. In agreement with this, in control platelets, monodansyl-cadaverine (MDC), a competitive amino-donor for TGs, inhibited fibrinogen binding induced by TRAP in a dose-dependent manner. Moreover, upon adhesion to fibrinogen, normal platelets incubated with MDC as well as FXIII-A-deficient platelets showed a distinct extension pattern with reduced lamellipodia and increased filopodia formation, suggesting a delay in spreading. CONCLUSIONS: These findings provide evidence for the direct involvement of cFXIII-dependent TG activity in the regulation of platelet functions.
Authors: Bettina Kárai; Zsuzsanna Hevessy; Eszter Szánthó; László Csáthy; Anikó Ujfalusi; Katalin Gyurina; István Szegedi; János Kappelmayer; Csongor Kiss Journal: Pathol Oncol Res Date: 2017-05-18 Impact factor: 3.201
Authors: Joanne L Mitchell; Ausra S Lionikiene; Steven R Fraser; Claire S Whyte; Nuala A Booth; Nicola J Mutch Journal: Blood Date: 2014-10-20 Impact factor: 22.113
Authors: Rolf P Kreutz; Glen Schmeisser; Andrea Schaffter; Sri Kanuri; Janelle Owens; Benjamin Maatman; Anjan Sinha; Elisabeth von der Lohe; Jeffrey A Breall Journal: TH Open Date: 2018-04
Authors: Zsuzsanna Z Orosz; Helga Bárdos; Amir H Shemirani; Ildikó Beke Debreceni; Riitta Lassila; Antti S Riikonen; Johanna A Kremer Hovinga; Theo G Seiler; Hendrika A van Dorland; Verena Schroeder; Zoltán Boda; László Nemes; Beatrice Früh Eppstein; Bence Nagy; Andrea Facskó; János Kappelmayer; László Muszbek Journal: Int J Mol Sci Date: 2019-11-27 Impact factor: 5.923