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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Interaction of cellular prion and stress-inducible protein 1 promotes neuritogenesis and neuroprotection by distinct signaling pathways

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Lopes, Marilene H. ; Hajj, Glaucia N. M. ; Muras, Angelita G. ; Mancini, Gabriel L. ; Castro, Rosa M. P. S. ; Ribeiro, Karina C. B. ; Brentani, Ricardo R. ; Linden, Rafael ; Martins, Vilma R. [9]
Número total de Autores: 9
Tipo de documento: Artigo Científico
Fonte: JOURNAL OF NEUROSCIENCE; v. 25, n. 49, p. 11330-11339, Dec. 2005.
Área do conhecimento: Ciências Biológicas - Bioquímica
Assunto(s):Proteínas   Príons   Quinases de proteína quinase ativadas por mitógeno

Understanding the physiological function of the cellular prion (PrPc) depends on the investigation of PrPc-interacting proteins. Stressinducible protein 1 (STI1) is a specific PrPc ligand that promotes neuroprotection of retinal neurons through cAMP-dependent protein kinaseA(PKA). Here,weexamined the signaling pathways and functional consequences of the PrPc interaction with STI1 in hippocampal neurons. Both PrPc and STI1 are abundantly expressed and highly colocalized in the hippocampus in situ, indicating that they can interact in vivo. Recombinant STI1 (His6-STI1) added to hippocampal cultures interacts with PrPc at the neuronal surface and elicits neuritogenesis in wild-type neurons but not in PrPc-null cells. This effect was abolished by antibodies against either PrPc or STI1 and was dependent on the STI1 domain that binds PrPc. Binding of these proteins induced the phosphorylation/activation of the mitogenactivated protein kinase, which was essential for STI1-promoted neuritogenesis. His6-STI1, but not its counterpart lacking the PrPc binding site, prevented cell death via PKA activation. These results demonstrate that two parallel effects of the PrPc-STI1 interaction, neuritogenesis and neuroprotection, are mediated by distinct signaling pathways. (AU)

Processo FAPESP: 03/13189-2 - Papel da proteína prion celular em processos fisiológicos e patológicos II
Beneficiário:Vilma Regina Martins
Linha de fomento: Auxílio à Pesquisa - Temático