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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
47
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pubmed:dateCreated |
2010-11-15
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pubmed:abstractText |
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 ?-bungarotoxin, a specific inhibitor for ?7 nicotinic acetylcholine receptor (?7nAChR), was able to block PrP(C)-STI1-mediated signaling, neuroprotection, and neuritogenesis. Importantly, when ?7nAChR 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)·?7nAChR complex to promote signaling and provide a novel potential target for modulation of the effects of prion protein in neurodegenerative diseases.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Heat-Shock Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinase 3,
http://linkedlifedata.com/resource/pubmed/chemical/PrPC Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Nicotinic,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Stip1 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/alpha7 nicotinic acetylcholine...
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
1083-351X
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:day |
19
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pubmed:volume |
285
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
36542-50
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pubmed:meshHeading |
pubmed-meshheading:20837487-Animals,
pubmed-meshheading:20837487-Apoptosis,
pubmed-meshheading:20837487-Blotting, Western,
pubmed-meshheading:20837487-Calcium Signaling,
pubmed-meshheading:20837487-Cell Proliferation,
pubmed-meshheading:20837487-Cells, Cultured,
pubmed-meshheading:20837487-Embryo, Mammalian,
pubmed-meshheading:20837487-Female,
pubmed-meshheading:20837487-Heat-Shock Proteins,
pubmed-meshheading:20837487-Hippocampus,
pubmed-meshheading:20837487-Humans,
pubmed-meshheading:20837487-Immunoprecipitation,
pubmed-meshheading:20837487-MAP Kinase Signaling System,
pubmed-meshheading:20837487-Male,
pubmed-meshheading:20837487-Mice,
pubmed-meshheading:20837487-Mice, Inbred C57BL,
pubmed-meshheading:20837487-Mitogen-Activated Protein Kinase 3,
pubmed-meshheading:20837487-Neurons,
pubmed-meshheading:20837487-PrPC Proteins,
pubmed-meshheading:20837487-Protein Binding,
pubmed-meshheading:20837487-RNA, Messenger,
pubmed-meshheading:20837487-Receptors, Nicotinic,
pubmed-meshheading:20837487-Recombinant Proteins,
pubmed-meshheading:20837487-Reverse Transcriptase Polymerase Chain Reaction
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pubmed:year |
2010
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pubmed:articleTitle |
Role of alpha7 nicotinic acetylcholine receptor in calcium signaling induced by prion protein interaction with stress-inducible protein 1.
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pubmed:affiliation |
Ludwig Institute for Cancer Research, Hospital Alemão Oswaldo Cruz, São Paulo 01323-903, Brazil.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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