The Ets transcription factor, Etv5, mediates biological response to NGF

FONTANET P, IRALA D, ALSINA F, HITA F, PARATCHA G, LEDDA F

Huerta Grande, Córdoba

Congreso; XXVI Congreso anual de la SOciedad Argentina de investigación en Neurociencias; 2011

Sociedad Argentina de INvestigación en Neurociencia

NGF is a member of the neurotrophins, a family of growth factors critical for the development and function of the nervous system. It was originally described as a survival and differentiation factor of sensory and sympathetic neurons. The physiological relevance of the in vitro effects of NGF on the survival of peripheral neurons has been substantiated by the reduction in the number of sensory and sympathethic neurons observed in NGF mutant mice. Two receptors have been identified for NGF: TrkA, high affinity receptor, and p75, low affinity receptor. Different signaling pathways are activated upon NGF binding to TrkA receptor, including those mediated by Ras/Mitogen activated kinase (MAPK), PI3-kinase (PI3K)/Akt and PLC γ. Using a cDNA microarray screening for new signaling mediators of NGF, we identified Ets variant 5 (Etv5). Etv5, also known as Erm (ets related molecule Pea3-like), belongs to the Pea3 (polyoma enhancer activator 3) subfamily of ETS transcription factors comprising three subfamily members, namely Pea3, Er81 and Erm. The Ets transcription factors are characterized by an evolutionary-conserved DNA-binding domain, which regulates the expression of a variety of cellular genes by binding specific purine-rich GGAA/T sequence in cooperation with other transcriptional factors and cofactors. While peripheral neurotrophic signals have been shown to direct the onset of expression of the ETS transcription factors Er81 and Pea3 in DRG sensory neurons and motor neuron pools several days after these neurons have become post-mitotic, the role of Etv5 has not been analyzed. On the other hand, mice carrying a targeted deletion of Etv5 are lethal at early embryonic stages, precluding the analysis of Etv5 function in neural development in these mutants. The aim of this study was to explore the role of Etv5 transcription factor in the biological response induced by NGF and its receptor TrkA. To this end, we used small hairpin RNA knock-down approach to block Etv5 function in PC12 cells. The data presented in this study suggest that the ETS transcription factor Etv5 has an essential role in the NGF-induced neuronal differentiation.