RGD Reference Report - G-protein-coupled receptor signaling components localize in both sarcolemmal and intracellular caveolin-3-associated microdomains in adult cardiac myocytes. - Rat Genome Database

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G-protein-coupled receptor signaling components localize in both sarcolemmal and intracellular caveolin-3-associated microdomains in adult cardiac myocytes.

Authors: Head, BP  Patel, HH  Roth, DM  Lai, NC  Niesman, IR  Farquhar, MG  Insel, PA 
Citation: Head BP, etal., J Biol Chem. 2005 Sep 2;280(35):31036-44. Epub 2005 Jun 16.
RGD ID: 1598749
Pubmed: (View Article at PubMed) PMID:15961389
DOI: Full-text: DOI:10.1074/jbc.M502540200

This study tests the hypothesis that G-protein-coupled receptor (GPCR) signaling components involved in the regulation of adenylyl cyclase (AC) localize with caveolin (Cav), a protein marker for caveolae, in both cell-surface and intracellular membrane regions. Using sucrose density fractionation of adult cardiac myocytes, we detected Cav-3 in both buoyant membrane fractions (BF) and heavy/non-buoyant fractions (HF); beta2-adrenergic receptors (AR) in BF; and AC5/6, beta1-AR, M4-muscarinic acetylcholine receptors (mAChR), mu-opioid receptors, and Galpha(s) in both BF and HF. In contrast, M2-mAChR, Galpha(i3), and Galpha(i2) were found only in HF. Immunofluorescence microscopy showed co-localization of Cav-3 with AC5/6, Galpha(s), beta2-AR, and mu-opioid receptors in both sarcolemmal and intracellular membranes, whereas M2-mAChR were detected only intracellularly. Immunofluorescence of adult heart revealed a distribution of Cav-3 identical to that in isolated adult cardiac myocytes. Upon immunoelectron microscopy, Cav-3 co-localized with AC5/6 and Galpha(s) in sarcolemmal and intracellular vesicles, the latter closely allied with T-tubules. Cav-3 immunoprecipitates possessed components that were necessary and sufficient for GPCR agonist-promoted stimulation and inhibition of cAMP formation. The distribution of GPCR, G-proteins, and AC with Cav-3 in both sarcolemmal and intracellular T-tubule-associated regions indicates the existence of multiple Cav-3-localized cellular microdomains for signaling by hormones and drugs in the heart.

Annotation

Gene Ontology Annotations    

Biological Process

Cellular Component

Molecular Function

Objects Annotated

Genes (Rattus norvegicus)
Adcy5  (adenylate cyclase 5)
Adcy6  (adenylate cyclase 6)
Adrb2  (adrenoceptor beta 2)
Cav3  (caveolin 3)
Chrm2  (cholinergic receptor, muscarinic 2)
Chrm4  (cholinergic receptor, muscarinic 4)
Gnai2  (G protein subunit alpha i2)
Gnai3  (G protein subunit alpha i3)
Gnas  (GNAS complex locus)
Oprm1  (opioid receptor, mu 1)

Objects referenced in this article
Gene Adrb1 adrenoceptor beta 1 Rattus norvegicus

Additional Information