Neuronal activity‐dependent nucleocytoplasmic shuttling of HDAC4 and HDAC5

• DOI: 10.1046/j.1471-4159.2003.01648.x
• Publication Date: 2010-07-16T07:16:19Z
• Authors: Sangeeta Chawla; Peter Vanhoutte; Fiona J. L. Arnold; Christopher L.‐H....; Hilmar Bading
• Keywords: Histone deacetylase 5; HDAC4; Nuclear export signal; Mef2

Abstract The class II histone deacetylases, HDAC4 and HDAC5, directly bind to repress myogenic transcription factors of the myocyte enhancer factor‐2 (MEF‐2) family thereby inhibiting skeletal myogenesis. During muscle differentiation, repression gene by MEF‐2/HDAC complexes is relieved due calcium/calmodulin‐dependent (CaM) kinase‐induced translocation HDAC5 cytoplasm. MEF‐2 proteins HDACs are also highly expressed in nervous system have been implicated neuronal survival differentiation. Here we investigated possibility that subcellular localization HDACs, thus their ability target genes, controlled synaptic activity neurones. We found that, cultured hippocampal neurones, dynamic signal‐regulated. Spontaneous electrical was sufficient for nuclear export but not HDAC5. cytoplasm induced following stimulation calcium flux through NMDA receptors or L‐type channels; glutamate bath application (stimulating extrasynaptic receptors) antagonized export. Activity‐induced nucleocytoplasmic shuttling both partially blocked CaM kinase inhibitor KN‐62 with being more sensitive inhibition than HDAC4. Thus, neurones specified activity; differences activation thresholds provides a mechanism input‐specific expression.