Prion Protein and Its Ligand Stress Inducible Protein 1 Regulate Astrocyte Development

Prion protein (PrPC) interaction with stress inducible protein 1 (STI1) mediates neuronal survival and differentiation. However, the function of PrPC in astrocytes has not been approached. In this study, we show that STI1 prevents cell death in wild-type astrocytes in a protein kinase A-dependent manner, whereas PrPC-null astrocytes were not affected by STI1 treatment. At embryonic day 17, cultured astrocytes and brain extracts derived from PrPC-null mice showed a reduced expression of glial fibrillary acidic protein (GFAP) and increased vimentin and nestin expression when compared with wild-type, suggesting a slower rate of astrocyte maturation in PrPC-null animals. Furthermore, PrPC-null astrocytes treated with STI1 did not differentiate from a flat to a process-bearing morphology, as did wild-type astrocytes. Remarkably, STI1 inhibited proliferation of both wild-type and PrPC-null astrocytes in a protein kinase C-dependent manner. Taken together, our data show that PrPC and STI1 are essential to astrocyte development and act through distinct signaling pathways.(C) 2009 Wiley-Liss, Inc.