Flavia R. S. Lima and Vilma R. Martins contributed to this work equally.
Prion protein and its ligand stress inducible protein 1 regulate astrocyte development
Article first published online: 25 FEB 2009
Copyright © 2009 Wiley-Liss, Inc.
Volume 57, Issue 13, pages 1439–1449, October 2009
How to Cite
Arantes, C., Nomizo, R., Lopes, M. H., Hajj, G. N. M., Lima, F. R. S. and Martins, V. R. (2009), Prion protein and its ligand stress inducible protein 1 regulate astrocyte development. Glia, 57: 1439–1449. doi: 10.1002/glia.20861
- Issue published online: 22 AUG 2009
- Article first published online: 25 FEB 2009
- Manuscript Accepted: 20 JAN 2009
- Manuscript Received: 3 DEC 2008
- FAPESP (Fundação de Amparo à Pesquisa do Estado de São Paulo)
- Howard Hughes Medical Institute. Grant Number: 03-13189-2
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. © 2009 Wiley-Liss, Inc.