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Título

A variant thrombasthenic phenotype associated with compound heterozygosity of integrin beta3-subunit: (Met124Val)beta3 alters the subunit dimerization rendering a decreased number of constitutive active alphaIIbbeta3 receptors

AutorGonzález-Manchón, Consuelo ; Butta, Nora ; Larrucea, Susana ; García Arias-Salgado, Elena ; Alonso, Sonia ; López, Angela; Parrilla, Roberto L.
Palabras clavePlatelets
αIIbβ3
thrombasthenia
β3 gain function mutation
Fecha de publicacióndic-2004
EditorSchattauer
CitaciónThrombosis and Haemostasis 92(6):1377-1386(2004)
ResumenWe report the analysis of a variant case of thrombasthenic phenotypethat is a compound heterozygote for two mutationslocated within the metal ion dependent adhesion site (MIDAS)of the β3 subunit.The patient inherited a maternal allele carryingthe Met124Val substitution and a paternal allele thatchanges Asp119 to Tyr. Phenotyping of the human platelet antigen1 (HPA-1) showed that the platelet αIIbβ3 complex in thepatient was mostly accounted for by the Asp 119Tyr allele thatdoes not bind to fibrinogen (Fg). The patient showed agonistinducedbinding of platelets to Fg but neither binding to PAC-1nor cell aggregation could be detected, most likely due to the minute expression (≤5%) of αIIb(124Val)β3 receptors. CHOcells expressing (124Val)β3 showed a diminished surfaceexpression of aIIbß3, enhanced adhesion to immobilized Fg,and spontaneous aggregation in the presence of soluble Fg, suggestingthat (124Val)β3 may confer constitutive activity to theαIIb(124Val)β3 receptors. A distinct feature of these cells is thefailure of DTT to enhance the binding to soluble Fg and the formationof cell aggregates. The substitution of (124Met)β3 byeither a polar or a positively charged amino acid restored thesurface exposure and function of the αIIbβ3 receptors whereasa negatively charged residue did not
Descripción12 páginas, 7 figuras, 1 tabla -- PAGS nros. 1377-1386
Versión del editorhttp://dx.doi.org/10.1160/TH04-06-0380
URIhttp://hdl.handle.net/10261/72831
DOI10.1160/TH04-06-0380
ISSN0340-6245
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