Expression and subcellular localization of thymosin beta15 following kainic acid treatment in rat brain

Abstract

Thymosin beta 15 (T beta 15) is a pleiotropic factor which exerts multiple roles in the development of nervous system and brain diseases. In this study, we found that the expressions of T beta 15 mRNA and protein were substantially increased in several brain regions including hippocampal formation and cerebral cortex, following kainic acid (KA)-evoked seizures in rat. Interestingly, a subset of cortex neurons exhibited nuclear T beta 15 immunoreactivity upon KA treatment. Furthermore, translocation of T beta 15 from cytosol to nuclei was observed in cultured neurons or HeLa cells during staurosporine (STS)-induced apoptosis, which was also verified by time-lapse imaging of YFP-tagged T beta 15. It appeared that localization of T beta 15 is restricted to the cytosol in normal condition by its G-actin-interacting domain, because site-directed mutagenesis of this region resulted in the nuclear localization of T beta 15 in the absence of STS treatment. To explore the role of nuclear T beta 15, we enforced T beta 15 to localize in the nuclei by fusion of T beta 15 with nuclear localization signal (NLS-T beta 15). However, overexpression of NLS-T beta 15 did not alter the viability of cells in response to STS treatment. Collectively, these results suggest that nuclear localization of T beta 15 is a controlled process during KA or STS stimulation, although its functional significance is yet to be clarified. (C) 2008 Elsevier Inc. All rights reserved.