Resumen de Análisis funcional de DREAM en los mecanismos de excitabilidad y viabilidad neuronal

Sofía María Domingo Vera

• DREAM (Downstream Regulatory Element Antagonist Modulator) is an EFhand protein highly expressed in the nervous system that plays different roles depending on its intracellular localization. In the nucleus, DREAM functions as a calcium-dependent transcriptional repressor. At the plasma membrane, DREAM (KChIP3) interacts with voltage-gated K channels regulating their activity.

  Here we use transgenic mice expressing a dominant active DREAM mutant (daDREAM) to study the function of DREAM in the control of calcium signals in neurons. At the plasma membrane, we found a role for DREAM in the modulation of NMDA-dependent synaptic transmission via interaction with the scaffolding protein PSD-95. Moreover, we characterized the interaction of DREAM with the poreforming subunit of the L-type voltage gated calcium channels. Through this interaction, DREAM enhances calcium entry upon depolarization. In the nucleus, DREAM regulates the transcription of some key genes involved in neuronal viability like BDNF, hrk and procaspase-9. All together, daDREAM transgenic neurons showed an increase in neuronal survival when challenged with both excitotoxic and apoptotic insults.

  We report that, through the control of both neuronal excitability and calciumdependent gene transcription, DREAM actively participates in neuroprotection.