Utrophins compensate for Dp71 absence in mdx3cv in adhered platelets.
Platelet adhesion is a critical step due to its hemostatic role in stopping bleeding after vascular damage. Short dystrophins are the most abundant dmd gene products in nonmuscle tissues, and in association with cytoskeleton proteins contribute to their intrinsic function; while utrophins are dystrophin-homologous related family proteins with structural and functional similarities. We previously demonstrated the presence of Dp71 isoforms, utrophins, and various dystrophin-associated proteins and their participation in cytoskeleton re-organization, filopodia and lamellipodia extension, and in centralizing cytoplasmic granules during the adhesion process of human platelets. To evaluate the morphologic changes and actin-based structures of mdx(3cv) platelets during the adhesion process, we compared the topographic distribution of Dp71d/Dp71Delta110(m) and dystrophin-associated protein in adhered platelets from dystrophic mdx(3cv) mouse. By confocal microscopy, we showed that absence of Dp71 isoforms in platelets from this animal model disrupted dystrophin-associated protein expression and distribution without modifying the platelet morphology displayed during the glass-adhesion process. By immunoprecipitation assays, we proved that up-regulated utrophins were associated with dystrophin-associated proteins to conform the dystrophin-associated protein complex corresponding to utrophins, which might compensate for Dp71 absence in mdx(3cv) platelets.
Cerecedo
Doris
D
Laboratorio de Hematobiología, Escuela Nacional de Medicina y Homeopatía, Instituto Politécnico Nacional (IPN), México, DF.
Mondragón
Ricardo
R
Candelario
Aurora
A
García-Sierra
Francisco
F
Mornet
Dominique
D
Rendón
Alvaro
A
Martínez-Rojas
Dalila
D
D000818:Animals; D001792:Blood Platelets / Q000502:physiology; D016189:Dystrophin / Q000502:physiology*; D049029:Dystrophin-Associated Proteins / Q000378:metabolism*; D051379:Mice; D018101:Mice, Inbred mdx; D010973:Platelet Adhesiveness / Q000502:physiology*; D015854:Up-Regulation; D049411:Utrophin / Q000502:physiology*
D016189:Dystrophin; D049029:Dystrophin-Associated Proteins; D049411:Utrophin; C085339:apo-dystrophin 1