Role of α7 Nicotinic Acetylcholine Receptor in Calcium Signaling Induced by Prion Protein Interaction with Stress-inducible Protein 1
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Role of α7 Nicotinic Acetylcholine Receptor in Calcium Signaling Induced by Prion Protein Interaction with Stress-inducible Protein 1
Autor:
Beraldo, Flavio H.
;
Arantes
, Camila
P
.
;
Santos, Tiago G.
;
Queiroz, Nicolle G.T.
;
Young, Kirk
;
Rylett, R. Jane
;
Markus, Regina
P
.
;
Prado, Marco A.M.
;
Martins, Vilma R.
Assuntos:
Heat Shock Protein
;
Molecular Bases of Disease
;
Neuron
;
Nicotinic Acetylcholine Receptors
;
Prions
;
Signal Transduction
É parte de:
The Journal of biological chemistry, 2010-11, Vol.285 (47),
p
.36542-36550
Descrição:
The prion protein (PrPC) is a conserved glycosylphosphatidylinositol-anchored cell surface protein expressed by neurons and other cells. Stress-inducible protein 1 (STI1) binds PrPC 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-PrPC engagement induces an increase in intracellular Ca2+ levels. This effect was not detected in PrPC-null neurons or wild-type neurons treated with an STI1 mutant unable to bind PrPC. Using a best candidate approach to test for potential channels involved in Ca2+ influx evoked by STI1-PrPC, we found that α-bungarotoxin, a specific inhibitor for α7 nicotinic acetylcholine receptor (α7nAChR), was able to block PrPC-STI1-mediated signaling, neuroprotection, and neuritogenesis. Importantly, when α7nAChR was transfected into HEK 293 cells, it formed a functional complex with PrPC and allowed reconstitution of signaling by PrPC-STI1 interaction. These results indicate that STI1 can interact with the PrPC·α7nAChR complex to promote signaling and provide a novel potential target for modulation of the effects of prion protein in neurodegenerative diseases.
Editor:
9650 Rockville Pike, Bethesda, MD 20814, U.S.A: Elsevier Inc
Idioma:
Inglês