This project will define what functions importin alpha proteins serve additional to their conventional role in selective cargo transport. Typically, importins localize predominantly in the cell cytoplasm to bind cargo for transport. We recently observed selected importin alpha proteins within the nucleus in particular physiological situations: in response to stress, and during specific stages of spermatogenesis. We propose this leads to altered chromatin function and gene transcription, through importin alpha interactions with chromatin and other nuclear proteins. This study will define a new mechanism by which cells change in response to stress signals (including oxidative stress) and during particular phases of development.