Vasopressin-Induced Cytoplasmic and Nuclear Calcium Signaling in Embryonic Cortical Astrocytes: Dynamics of Calcium and Calcium-Dependent Kinase Translocation

摘要

The present study sought to determine the downstream consequences of V1a vasopressin receptor (V1aR) activation of Ca²⁺ signaling in cortical astrocytes. Results of these analyses demonstrated that V1aR activation led to a marked increase in both cytoplasmic and nuclear Ca²⁺. We also investigated V1aR activation of Ca²⁺-activated signaling kinases, protein kinase C (PKC), Ca²⁺/calmodulin-dependent protein kinase II (CaMKII), and the mitogen-activated protein (MAP) kinases [MAPK and extracellular signal-regulated kinases 1 and 2 (ERK1/2)], their localization within cytoplasmic and nuclear compartments, and activation of their downstream nuclear target, the transcription factor cAMP response element-binding protein (CREB). Results of these analyses demonstrated that V1aR activation led to a significant rise in PKC, CaMKII, and ERK1/2 activation, with CaMKII and ERK1/2 demonstrating dynamic transport between cytoplasmic and nuclear compartments. Although no evidence of PKC translocation was apparent, PKC and CaMKs were required for activation and nuclear translocation of ERK1/2. Subsequent to CaMKII and ERK1/2 translocation to the nucleus, CREB activation occurred and was found to be dependent on upstream activation of ERK1/2 and CaMKs. These data provide the first systematic analysis of the V1aR-induced Ca²⁺ signaling cascade in cortical astrocytes. In addition, results of this study introduce a heretofore unknown effect of vasopressin, dynamic Ca²⁺ signaling between the cytoplasm and nucleus that leads to comparable dynamics of kinase activation and shuttling between cytoplasmic and nuclear compartments. Implications for development and regeneration induced by V1aR activation of CREB-regulated gene expression in cortical astrocytes are discussed.