INVESTIGADORES
FRANCO Diana Lorena
congresos y reuniones científicas
Título:
Characterization of ena/VASP domains with dominat negative function
Autor/es:
HERNÁNDEZ MV, FRANCO DL, AND CERIANI MF.
Lugar:
Huerta Grande, Cordoba
Reunión:
Congreso; XXVI Congreso Anual de la Sociedad Argentina de Investigación en Neurociencias; 2011
Institución organizadora:
Sociedad Argentina de Neurociencias
Resumen:
Neurodegeneration is a process known to occur in metazoans. In previous work we found that the gene enabled (ena), encoding a protein involved in cytoskeleton remodeling, is implicated in progressive neurodegeneration in Drosophila. Silencing ena ortholog genes (the ena/VASP family) in mouse hippocampal neurons triggered neurite retraction and concominant neuronal cell death through an apoptotic pathway. Since our ultimate goal is to confirm these results in a mouse model of late onset progressive neurodegeneration through deregulation of ena/VASP family members, we characterized potential dominant negative (DN) versions to identify the most effective one. Ena/VASP proteins share three well-defined domains, the EVH1 domain, a central proline-rich region, and EVH2. Thus we analyzed the expression of EVH1-GFP, EVH2-GFP and GFP (control) in transfected NIH 3T3 cells. Both constructs delocalized VASP with variable efficiency, however none of them affected Mena localization. Preliminary results after DN overexpression in mouse hippocampal neurons led to neurite retraction, recreating what was observed with RNAi pools. Interestingly, EVH1 displayed the most potent inhibition compared to EVH2, suggesting the EVH1 domain is a good candidate to generate an inducible transgenic model.