Activity-dependent translocation of neurogranin to neuronal nuclei

Alberto Garrido-García , Beatriz Andrés-Pans , Lara Duran-Trio , F. Javier Díez-Guerra (1)

1 Depto Biología Molecular, Centro de Biología Molecular Severo Ochoa (CSIC-UAM)

Long-term changes of synaptic plasticity depend on protein synthesis and transcription. Neurogranin (Ng) is a small protein concentrated at dendrites and spines of forebrain neurons, involved in synaptic plasticity through the regulation of calmodulin (CaM) mediated signalling. Ng presents a central IQ motif that mediates its binding to CaM and phosphatidic acid (PA) and that can be phosphorylated by protein kinase C (PKC). Here, we report that Ng displays a strong nuclear localization when expressed in cell lines and hippocampal neurons, either alone or fused to green fluorescent protein (GFP-Ng). Further, using subcellular fractionation and immunocytochemical techniques, we were able to localize endogenous Ng in the nuclei of rat forebrain neurons. Nuclear localization of Ng depends on its IQ motif and is reduced by binding to cytoplasmic CaM. Also, PKC stimulation induces a transient nuclear translocation of Ng in acute hippocampal slices. A similar translocation is observed in neurons of the cerebral cortex and hippocampus after the induction of generalized seizures in adult rats. In summary, the data presented here show that a fraction of rat brain Ng is localized in the neuronal nuclei and that synaptic activity regulates its translocation from the cytoplasm. The possible involvement of Ng in the regulation of intranuclear Ca2+/CaM dependent signalling and gene expression is discussed.

Mots clés: Life Sciences

Alberto Garrido-García, Beatriz Andrés-Pans, Lara Duran-Trio, F. Javier Díez-Guerra. Activity-dependent translocation of neurogranin to neuronal nuclei. Biochemical Journal, 2009, 424 (3), pp.419-429. ⟨10.1042/BJ20091071⟩. ⟨hal-00479228⟩