Back to Search
Start Over
Role of alpha7 nicotinic acetylcholine receptor in calcium signaling induced by prion protein interaction with stress-inducible protein 1.
- Source :
-
The Journal of biological chemistry [J Biol Chem] 2010 Nov 19; Vol. 285 (47), pp. 36542-50. Date of Electronic Publication: 2010 Sep 13. - Publication Year :
- 2010
-
Abstract
- The prion protein (PrP(C)) is a conserved glycosylphosphatidylinositol-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 PrP(C)-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 bind PrP(C). Using a best candidate approach to test for potential channels involved in Ca(2+) influx evoked by STI1-PrP(C), we found that α-bungarotoxin, a specific inhibitor for α7 nicotinic acetylcholine receptor (α7nAChR), was able to block PrP(C)-STI1-mediated signaling, neuroprotection, and neuritogenesis. Importantly, when α7nAChR was transfected into HEK 293 cells, it formed a functional complex with PrP(C) and allowed reconstitution of signaling by PrP(C)-STI1 interaction. These results indicate that STI1 can interact with the PrP(C)·α7nAChR complex to promote signaling and provide a novel potential target for modulation of the effects of prion protein in neurodegenerative diseases.
- Subjects :
- Animals
Apoptosis
Blotting, Western
Cell Proliferation
Cells, Cultured
Embryo, Mammalian cytology
Embryo, Mammalian metabolism
Female
Heat-Shock Proteins genetics
Hippocampus cytology
Humans
Immunoprecipitation
MAP Kinase Signaling System physiology
Male
Mice
Mice, Inbred C57BL
Mitogen-Activated Protein Kinase 3 genetics
Mitogen-Activated Protein Kinase 3 metabolism
Neurons cytology
Protein Binding
RNA, Messenger genetics
Receptors, Nicotinic genetics
Recombinant Proteins genetics
Recombinant Proteins metabolism
Reverse Transcriptase Polymerase Chain Reaction
alpha7 Nicotinic Acetylcholine Receptor
Calcium Signaling physiology
Heat-Shock Proteins metabolism
Hippocampus metabolism
Neurons metabolism
PrPC Proteins physiology
Receptors, Nicotinic metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1083-351X
- Volume :
- 285
- Issue :
- 47
- Database :
- MEDLINE
- Journal :
- The Journal of biological chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 20837487
- Full Text :
- https://doi.org/10.1074/jbc.M110.157263