The role of {alpha}7 nicotinic acetylcholine receptor in calcium signaling induced by prion protein interaction with stress inducible protein 1.
Summary of "The role of {alpha}7 nicotinic acetylcholine receptor in calcium signaling induced by prion protein interaction with stress inducible protein 1."
The prion protein (PrP(C)) is a conserved glycosylphosphatidylinositol (GPI)-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 αbungarotoxin, 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 provides a novel potential target for modulation of the effects of prion protein in neurodegenerative diseases.
Affiliation
Robarts Research Institute, Canada;
Journal Details
This article was published in the following journal.
Name: The Journal of biological chemistry
ISSN: 1083-351X
Pages:
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/20837487
- DOI: http://dx.doi.org/10.1074/jbc.M110.157263
Medical and Biotech [MESH] Definitions
Receptor, Bradykinin B1
A subtype of bradykinin receptor that is induced in response to INFLAMMATION. It may play a role in chronic inflammation and has a high specificity for KININS lacking the C-terminal ARGININE such as des-Arg(10)-kallidin and des-Arg(9)-bradykinin. The receptor is coupled to G-PROTEIN, GQ-G11 ALPHA FAMILY and G-PROTEIN, GI-GO ALPHA FAMILY signaling proteins.
Glucocorticoid-induced Tnfr-related Protein
A member of the TNF receptor family that was initially identified as a DEXAMETHASONE-induced protein from a T-CELL line. It may play a role in regulating APOPTOSIS and modulating immune response by T-lymphocytes. Signaling by the activated receptor occurs through its association with TNF RECEPTOR-ASSOCIATED FACTORS.
Bungarotoxins
Neurotoxic proteins from the venom of the banded or Formosan krait (Bungarus multicinctus, an elapid snake). alpha-Bungarotoxin blocks nicotinic acetylcholine receptors and has been used to isolate and study them; beta- and gamma-bungarotoxins act presynaptically causing acetylcholine release and depletion. Both alpha and beta forms have been characterized, the alpha being similar to the large, long or Type II neurotoxins from other elapid venoms.
Nicotinic Antagonists
Drugs that bind to nicotinic cholinergic receptors (RECEPTORS, NICOTINIC) and block the actions of acetylcholine or cholinergic agonists. Nicotinic antagonists block synaptic transmission at autonomic ganglia, the skeletal neuromuscular junction, and at central nervous system nicotinic synapses.
Tnf Receptor-associated Factor 4
A widely expressed member of the TNF receptor-associated family that may play a role in neuronal development and EMBRYOGENESIS. Although TNF receptor-associated factor 4 does not strongly associate with TUMOR NECROSIS FACTOR RECEPTORS it may be a signaling partner with the GLUCOCORTICOID-INDUCED TNFR-RELATED PROTEIN that plays a role in the activation of JNK MITOGEN-ACTIVATED PROTEIN KINASES and NF-KAPPA B.
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