NR AXSH
AU Martins,V.R.; Arantes,C.P.; Lopes,M.H.; Hajj,G.N.M.; Lima,F.R.S.; Porto-Carreiro,I.; Linden,R.; Prado,M.A.
TI Stress Inducible Protein 1 is Released by Astrocytes in Exosome Vesicles Acting as a Cellular Prion Protein-Dependent Neurotrophic Factor
QU International Conference - Prion 2007 (26.-28.9.2007) Edinburgh International Conference Centre, Edinburgh, Scotland, UK - Book of Abstracts: Pathology and Pathogenesis P03.93
IA http://www.prion2007.com/pdf/Prion Book of Abstracts.pdf
PT Konferenz-Poster
AB
The physiological functions of cellular prion protein (PrPc) are under intense investigation. We have described that PrPc binds to Stress Inducible Protein 1 (STI1) inducing neuronal differentiation via Erk phosphorilation. STI1 can be secreted by astrocytes, even though it lacks a secretory signal sequence. We examined whether exosomes contribute to STI1 release. Exosomes were purified from conditioned medium (CM) from wild-type (Prnp+/+) and PrPc ablated (Prnp0/0) astrocytes. The exosomal fraction purification was evaluated by western blot using positive markers such as transferrin receptor, HSP70 and HSP90 and by measuring exosome associated acetylcholinesterase activity. Equal amounts of STI1 were detected in exosomal fractions from Prnp+/+ and Prnp0/0 astrocytes. Additionally, STI1 secretion was not affected when astrocytes were treated with Brefeldin A or Monensin indicating that this mechanism is independent on classical secretory pathways. When expressed and secreted by astrocytes as a fusion protein (GFP-STI1) STI1 binds to the neuronal surface and is internalized. Moreover, exosomes prepared from CM derived from atrocytes activate Erk signaling pathway in Prnp+/+ hippocampal neurons but not in Prnp0/0 ones and an anti-STI1 antibody blocks this activation. Therefore, STI1 is a neurotrophic factor secreted by astrocytes in exosome vesicles and its interaction with PrPc at the neuronal surface triggers signaling pathways associated with neuronal differentiation.
Supported by Fundação de Amparo a Pesquisa do Estado de São Paulo & Howard Hughes Medical Institute
AD V.R. Martins, C.P. Arantes, M.H. Lopes, G.N. Hajj, Ludwig Institute for Cancer Research, Brazil; F.R.S. Lima, Instituto de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Brazil; I. Porto-Carreiro, R. Linden, Instituto de Biofísica Carlos Chagas Filho, Brazil; M.A. Prado, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Brazil
SP englisch
PO Schottland