C3G regulates megakaryocytic differentiation and pro-platelet formation in mice

Autor: Ortiz-Rivero, Sara, Gutiérrez-Herrero, Sara, Martín-Granado, Víctor, González-Porras, José R., Porras, Almudena, Guerrero Arroyo, María del Carmen
Rok vydání: 2016
Zdroj: Digital.CSIC. Repositorio Institucional del CSIC
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Popis: Resumen del póster presentado al XXXIX Congreso de la Sociedad Española de Bioquímica y Biología Molecular, celebrado en Salamanca del 5 al 8 de septiembre de 2016.
C3G is an activator of members of the Rap subfamily of Ras proteins. Several studies suggest that C3G plays a role in different processes of differentiation acting through its main target Rap1. C3G is induced during neural differentiation and monocytic differentiation to macrophages. Similarly, an increase in C3G protein levels and its association with Crk is required for adipocyte differentiation. There are also evidences supporting the involvement of C3G in the differentiation of megakaryocytes to platelets through Rap1 activation, although its function in early stages of megakaryocytic differentiation has not yet been addressed. Using transgenic mouse models for C3G and C3GΔCat (C3G mutant lacking the GEF domain), where the transgenes are expressed under the control of the megakaryocyte and platelet specific PF4 gene promoter, we have found that C3G plays a role in the differentiation of immature hematopoietic cells to megakaryocytes. Bone marrow cells from transgenic C3G, but not those from transgenic C3GΔCat mice, showed increased CD41 and CD61 expression upon thrombopoietin (TPO) treatment. Polyploidization analysis supports the hypothesis of a positive role of C3G in megakaryocytic differentiation. Thus, C3G overexpression increased the levels of CD41+ megakaryocytes with 16N and 32N ploidy. In addition, preliminary studies using fresh bone marrow explants, incubated with Tyrode´s Buffer containing 5% mouse serum, showed an increased migration from the osteoblastic niche to the vascular niche and an enhanced ability to form pro-platelets in C3G transgenic megakaryocytes, as compared to wild-type ones. These results suggest the participation of C3G in different key aspects of megakaryopoiesis by a mechanism mediated by its GEF activity.
Databáze: OpenAIRE
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