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Role Of Alpha 7 Nicotinic Acetylcholine Receptor In Calcium Signaling Induced By Prion Protein Interaction With Stress-Inducible Protein 1, Flavio H. Beraldo, Camila P. Arantes, Tiago G. Santos, Nicolle G. T. Queiroz, Kirk Young, Jane R. Rylett, Regina P. Markus, Marco A. M. Prado, Vilma R. Martins

Anatomy and Cell Biology Publications

The prion protein (PrP(C)) is a conserved glycosylphosphatidyl-inositol-anchored cell surface protein expressed by neurons and other cells. Stress-inducible protein 1 (STI1) binds PrP(C) extracellularly, and this activated signaling complex promotes neuronal differentiation and neuroprotection via the extracellular signal-regulated kinase 1 and 2 (ERK1/2) and cAMP-dependent protein kinase 1 (PKA) pathways. However, the mechanism by which the PrPC-STI1 interaction transduces extracellular signals to the intracellular environment is unknown. We found that in hippocampal neurons, STI1-PrP(C) engagement induces an increase in intracellular Ca(2+) levels. This effect was not detected in PrP(C)-null neurons or wild-type neurons treated with an STI1 mutant unable to …