New insights into the expression and role of platelet factor XIII-A.
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.


OBJECTIVE
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.
Department of Cellular and Molecular Medicine, Centro de Investigaciones Biológicas (CSIC), Madrid, Spain.
A
A
Jayo
I
I
Conde
P
P
Lastres
V
V
Jiménez-Yuste
C
C
González-Manchón
D000328:Adult; D001483:Base Sequence; D001792:Blood Platelets / Q000201:enzymology / Q000378:metabolism*; D015153:Blotting, Western; D002675:Child, Preschool; D017931:DNA Primers; D026122:Factor XIIIa / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D009154:Mutation; D015539:Platelet Activation; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics
D017931:DNA Primers; D012333:RNA, Messenger; D026122:Factor XIIIa