Does ENA regulate SRF activity? a possible mechanism to explain the cell death induced by ENA downregulation

D. LORENA FRANCO, MARIANA V. HERNANDEZ & M. FERNANDA CERIANI

Huerta Grande, Cordoba

Congreso; XXVII Congreso Anual de la Sociedad Argentina de Investigación en Neurociencias; 2012

Sociedad Argentina de Neurociencias

Does ENA regulate SRF activity? a possible mechanism to explain the cell death induced by ENA downregulation. D. Lorena Franco, Mariana V. Hernandez & M. Fernanda Ceriani. Laboratorio de Genética del Comportamiento. Fundación Instituto Leloir, IIB-BA/CONICETNeuronal polarity is essential for input?output processing and appropriate flow of information in neuronal networks, contributing to the correct function of the nervous system. The complex and polarized morphology of neurons is maintained and dynamically modified by microtubules and the actin cytoskeleton. Among actin regulatory proteins, ENA/VASP is a conserved family which is critical for both filopodia formation and elongation. We have previously demonstrated that ENA/VASP downregulation in mouse hippocampal neurons generate axonal retraction, which subsequently induces neuronal death through an apoptotic mechanism. To further characterize the mechanism of neuronal death triggered by ena in vivo we now investigate its interaction with blistered (bs), the fly ortholog of SRF. SRF is a transcription factor regulated by actin levels and plays an important role in proliferation and survival. We hypothesized that changes in the dynamics of the actin cytoskeleton, produced by ena silencing, modulates the activity of the transcriptional cofactor MRTF, which regulates the activity of BS. To study this hypothesis we are performing behavioral and molecular assays through deregulation of bs expression in the context of reduced ena. These results will shed light on how reduced ENA levels induce neuronal death.