RGD Reference Report - Nicotinic acetylcholine receptor alpha 7 regulates cAMP signal within lipid rafts. - Rat Genome Database

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Nicotinic acetylcholine receptor alpha 7 regulates cAMP signal within lipid rafts.

Authors: Oshikawa, J  Toya, Y  Fujita, T  Egawa, M  Kawabe, J  Umemura, S  Ishikawa, Y 
Citation: Oshikawa J, etal., Am J Physiol Cell Physiol. 2003 Sep;285(3):C567-74. Epub 2003 May 14.
RGD ID: 1600980
Pubmed: PMID:12748066   (View Abstract at PubMed)
DOI: DOI:10.1152/ajpcell.00422.2002   (Journal Full-text)

Neuronal nicotinic acetylcholine receptors (nAChRs) are made of multiple subunits with diversified functions. The nAChR alpha 7-subunit has a property of high Ca2+ permeability and may have specific functions and localization within the plasma membrane as a signal transduction molecule. In PC-12 cells, fractionation by sucrose gradient centrifugation revealed that nAChR alpha 7 existed in low-density, cholesterol-enriched plasma membrane microdomains known as lipid rafts where flotillin also exists. In contrast, nAChR alpha 5- and beta2-subunits were located in high-density fractions, out of the lipid rafts. Type 6 adenylyl cyclase (AC6), a calcium-inhibitable isoform, was also found in lipid rafts and was coimmunoprecipitated with nAChR alpha 7. Cholesterol depletion from plasma membranes with methyl-beta-cyclodextrin redistributed nAChR alpha 7 and AC6 diffusely within plasma membranes. Nicotine stimulation reduced forskolin-stimulated AC activity by 35%, and this inhibition was negated by either treatment with alpha-bungarotoxin, a specific antagonist of nAChR alpha 7, or cholesterol depletion from plasma membranes. The effect of cholesterol depletion was negated by the addition of cholesterol. These data suggest that nAChR alpha 7 has a specific membrane localization relative to other nAChR subunits and that lipid rafts are necessary to localize nAChR alpha 7 with AC within plasma membranes. In addition, nAChR alpha 7 may regulate the AC activity via Ca2+ within lipid rafts.

Gene Ontology Annotations    Click to see Annotation Detail View

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
adenylate cyclase binding  IPIAdcy6 (Rattus norvegicus)1600980 RGD 
signaling receptor binding  IPIChrna7 (Rattus norvegicus)1600980 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Adcy6  (adenylate cyclase 6)
Chrna7  (cholinergic receptor nicotinic alpha 7 subunit)

Objects referenced in this article
Gene Adcy3 adenylate cyclase 3 Rattus norvegicus
Gene Chrna5 cholinergic receptor nicotinic alpha 5 subunit Rattus norvegicus
Gene Chrnb2 cholinergic receptor nicotinic beta 2 subunit Rattus norvegicus

Additional Information