Online citations, reference lists, and bibliographies.
← Back to Search

Differential Targeting Of Beta -adrenergic Receptor Subtypes And Adenylyl Cyclase To Cardiomyocyte Caveolae. A Mechanism To Functionally Regulate The CAMP Signaling Pathway.

V. Rybin, X. Xu, M. Lisanti, S. Steinberg
Published 2000 · Biology, Medicine

Cite This
Download PDF
Analyze on Scholarcy
Differential modes for beta(1)- and beta(2)-adrenergic receptor (AR) regulation of adenylyl cyclase in cardiomyocytes is most consistent with spatial regulation in microdomains of the plasma membrane. This study examines whether caveolae represent specialized subdomains that concentrate and organize these moieties in cardiomyocytes. Caveolae from quiescent rat ventricular cardiomyocytes are highly enriched in beta(2)-ARs, Galpha(i), protein kinase A RIIalpha subunits, caveolin-3, and flotillins (caveolin functional homologues); beta(1)-ARs, m(2)-muscarinic cholinergic receptors, Galpha(s), and cardiac types V/VI adenylyl cyclase distribute between caveolae and other cell fractions, whereas protein kinase A RIalpha subunits, G protein-coupled receptor kinase-2, and clathrin are largely excluded from caveolae. Cell surface beta(2)-ARs localize to caveolae in cardiomyocytes and cardiac fibroblasts (with markedly different beta(2)-AR expression levels), indicating that the fidelity of beta(2)-AR targeting to caveolae is maintained over a physiologic range of beta(2)-AR expression. In cardiomyocytes, agonist stimulation leads to a marked decline in the abundance of beta(2)-ARs (but not beta(1)-ARs) in caveolae. Other studies show co-immunoprecipitation of cardiomyocytes adenylyl cyclase V/VI and caveolin-3, suggesting their in vivo association. However, caveolin is not required for adenylyl cyclase targeting to low density membranes, since adenylyl cyclase targets to low buoyant density membrane fractions of HEK cells that lack prototypical caveolins. Nevertheless, cholesterol depletion with cyclodextrin augments agonist-stimulated cAMP accumulation, indicating that caveolae function as negative regulators of cAMP accumulation. The inhibitory interaction between caveolae and the cAMP signaling pathway as well as domain-specific differences in the stoichiometry of individual elements in the beta-AR signaling cascade represent important modifiers of cAMP-dependent signaling in the heart.
This paper references
Contribution of caveolin protein abundance to augmented nitric oxide signaling in conscious dogs with pacing-induced heart failure.
J. Hare (2000)
Regulation of cAMP-mediated Signal Transduction via Interaction of Caveolins with the Catalytic Subunit of Protein Kinase A*
B. Razani (1999)
Specific activation of adenylyl cyclase V by a purinergic agonist
M. Pucéat (1998)
Gravin-mediated Formation of Signaling Complexes in β2-Adrenergic Receptor Desensitization and Resensitization*
F. Lin (2000)
The molecular basis for distinct beta-adrenergic receptor subtype actions in cardiomyocytes.
S. Steinberg (1999)
Efficacy of beta 1-adrenergic receptors is lower than that of beta 2-adrenergic receptors.
F. Levy (1993)
Internalization of beta-adrenergic receptor in A431 cells involves non-coated vesicles.
G. Raposo (1989)
Compartmentation of cAMP in adult canine ventricular myocytes. Relation to single-cell free Ca2+ transients.
C. Hohl (1991)
cAMP-dependent protein kinase: framework for a diverse family of regulatory enzymes.
S. Taylor (1990)
Characterization of caveolin-rich membrane domains isolated from an endothelial-rich source: implications for human disease
M. Lisanti (1994)
Redistribution of muscarinic acetylcholine receptors on human fibroblasts induced by regulatory ligands
G. Raposo (1987)
A Peptide Derived from a β2-Adrenergic Receptor Transmembrane Domain Inhibits Both Receptor Dimerization and Activation*
T. Hébert (1996)
The adenylyl cyclases as integrators of transmembrane signal transduction.
Y. Ishikawa (1997)
Baculovirus-based Expression of Mammalian Caveolin in Sf21 Insect Cells
S. Li (1996)
Dynamic Targeting of the Agonist-stimulated m2 Muscarinic Acetylcholine Receptor to Caveolae in Cardiac Myocytes*
O. Féron (1997)
Thrombin modulates phosphoinositide metabolism, cytosolic calcium, and impulse initiation in the heart.
S. Steinberg (1991)
Src tyrosine kinases, Galpha subunits, and H-Ras share a common membrane-anchored scaffolding protein, caveolin. Caveolin binding negatively regulates the auto-activation of Src tyrosine kinases.
S. Li (1996)
Flotillin and Epidermal Surface Antigen Define a New Family of Caveolae-associated Integral Membrane Proteins*
P. Bickel (1997)
Regulation of G Protein-coupled Receptor Kinases by Caveolin*
C. Carman (1999)
Co-purification and Direct Interaction of Ras with Caveolin, an Integral Membrane Protein of Caveolae Microdomains
Kenneth S. Song (1996)
Purification and characterization of smooth muscle cell caveolae
W. Chang (1994)
β-Arrestin-Dependent Formation of β2 Adrenergic Receptor-Src Protein Kinase Complexes
L. Luttrell (1999)
Caveolins, a Family of Scaffolding Proteins for Organizing “Preassembled Signaling Complexes” at the Plasma Membrane*
Tetsuji Okamoto (1998)
Flotillins/Cavatellins Are Differentially Expressed in Cells and Tissues and Form a Hetero-oligomeric Complex with Caveolins in Vivo
D. Volonté (1999)
Novel adenovirus component system that transfects cultured cardiac cells with high efficiency.
T. Kohout (1996)
Cloning of the cDNA for the human beta 1-adrenergic receptor.
T. Frielle (1987)
Beta 1- and beta 2-adrenergic receptor-mediated adenylate cyclase stimulation in nonfailing and failing human ventricular myocardium.
M. Bristow (1989)
Effects of low density lipoproteins and mevinolin on sympathetic responsiveness in cultured chick atrial cells. Regulation of beta-adrenergic receptors and alpha s.
J. Barnett (1989)
Extraction of cholesterol with methyl-beta-cyclodextrin perturbs formation of clathrin-coated endocytic vesicles.
S. K. Rodal (1999)
Signaling properties and functions of two distinct cardiomyocyte protease-activated receptors.
A. Sabri (2000)
Downregulation of caveolin expression by cAMP signal.
M. Yamamoto (1999)
Signal transducing molecules and glycosyl-phosphatidylinositol-linked proteins form a caveolin-rich insoluble complex in MDCK cells
M. Sargiacomo (1993)
Low density lipoproteins induce parasympathetic responsiveness in embryonic chick ventricular myocytes in parallel with a coordinate increase in expression of genes coding for the M2 muscarinic receptor, G alpha i2, and the acetylcholine-sensitive K+ channel.
A. P. Gadbut (1994)
Selective enhancement of beta-adrenergic receptor signaling by overexpression of adenylyl cyclase type 6: colocalization of receptor and adenylyl cyclase in caveolae of cardiac myocytes.
R. Ostrom (2000)
Protein kinase C isoform expression and regulation in the developing rat heart.
V. Rybin (1994)
Membrane organization in G‐protein mechanisms
R. Neubig (1994)
Caveolae and sorting in the trans‐Golgi network of epithelial cells.
P. Dupree (1993)
Organization of G proteins and adenylyl cyclase at the plasma membrane.
C. Huang (1997)
Beta 1- and beta 2-adrenergic receptors display subtype-selective coupling to Gs.
S. Green (1992)
Signal Transduction via Glycosyl Phosphatidylinositol-anchored Proteins in T Cells Is Inhibited by Lowering Cellular Cholesterol*
T. Stulnig (1997)
A proline-rich region of the third intracellular loop imparts phenotypic beta 1-versus beta 2-adrenergic receptor coupling and sequestration.
S. A. Green (1994)
Activated protein kinase C isoforms target to cardiomyocyte caveolae : stimulation of local protein phosphorylation.
V. Rybin (1999)
Induction of caveolin during adipogenesis and association of GLUT4 with caveolin-rich vesicles
P. Scherer (1994)
Colocalization of β‐adrenergic receptors and caveolin within the plasma membrane
C. Schwencke (1999)
Acute cholesterol depletion inhibits clathrin-coated pit budding.
A. Subtil (1999)
Receptors for dopamine and somatostatin: formation of hetero-oligomers with enhanced functional activity.
M. Rocheville (2000)
Compartments of cyclic AMP and protein kinase in mammalian cardiomyocytes.
I. L. Buxton (1983)
Targeted disruption of the mouse beta1-adrenergic receptor gene: developmental and cardiovascular effects.
D. Rohrer (1996)
A detergent-free method for purifying caveolae membrane from tissue culture cells.
E. Smart (1995)

This paper is referenced by
Sequestration of Epidermal Growth Factor Receptors in Non-caveolar Lipid Rafts Inhibits Ligand Binding*
Kirstine Roepstorff (2002)
PDE3 inhibition in dilated cardiomyopathy: reasons to reconsider.
M. Movsesian (2003)
Altered cAMP-mediated signalling and its role in the pathogenesis of dilated cardiomyopathy.
M. Movsesian (2004)
Role of caveolae in ouabain-induced proliferation of cultured vascular smooth muscle cells of the synthetic phenotype.
Lijun Liu (2004)
Renal Na+-K+-Cl- cotransporter activity and vasopressin-induced trafficking are lipid raft-dependent.
P. Welker (2008)
Cell Signaling Coupled Receptor Oligomerization : Implications for G Protein Activation and - G Protein
Gerda Breitwieser (2013)
G protein-membrane interactions I: Gαi1 myristoyl and palmitoyl modifications in protein-lipid interactions and its implications in membrane microdomain localization.
R. Alvarez (2015)
Phosphatidylinositol 3-Kinase Offsets cAMP-Mediated Positive Inotropic Effect via Inhibiting Ca 2 Influx in Cardiomyocytes
V. Leblais (2004)
Ca2+ currents in cardiac myocytes: Old story, new insights.
F. Brette (2006)
G protein-coupled receptor oligomerization: implications for G protein activation and cell signaling.
G. Breitwieser (2004)
Dynamique Spatiotemporelle de la protéine kinase AMPc dépendante dans les myocytes cardiaques
Zeineb Haj Slimane Ammar (2012)
Delayed cardioprotection by inhaled anesthetics.
P. Pagel (2011)
Role of Phosphodiesterases in Cyclic Nucleotide Compartmentation in Cardiac Myocytes
A. Abi-gerges (2006)
Lipid rafts constrain basal alpha(1A)-adrenergic receptor signaling by maintaining receptor in an inactive conformation.
Beilei Lei (2009)
Molecular Dynamics and Docking Simulation Studies of Human Voltage Gated Sodium Channel against Neurotoxins
Vandana Saini (2016)
The NK1 Receptor Localizes to the Plasma Membrane Microdomains, and Its Activation Is Dependent on Lipid Raft Integrity*
K. Monastyrskaya (2005)
Loss of caveolin-3-dependent regulation of ICa in rat ventricular myocytes in heart failure
S. M. Bryant (2018)
Knockout of adenylyl cyclase isoform 5 or 6 differentially modifies the β1-adrenoceptor-mediated inotropic response.
Marie-Victoire Cosson (2019)
Presence of Androgen Receptor Variant in Neuronal Lipid Rafts
Jo Garza-Contreras (2017)
Mechanisms of labour—biochemical aspects
A. Bernal (2003)
Neurohumoral Control of Sinoatrial Node Activity and Heart Rate: Insight From Experimental Models and Findings From Humans
E. Macdonald (2020)
Relaxin Stimulates cAMP Production in MCF‐7 Cells upon Overexpression of Type V Adenylyl Cyclase
B. Nguyen (2005)
Localization of neutral ceramidase in caveolin‐enriched light membranes of murine endothelial cells
E. Romiti (2001)
Type 5 Adenylyl Cyclase Disruption Alters Not Only Sympathetic But Also Parasympathetic and Calcium-Mediated Cardiac Regulation
S. Okumura (2003)
A guide to drug discovery: Predicting therapeutic value in the lead optimization phase of drug discovery
T. Kenakin (2003)
The Role of Phosphodiesterase-2 in Psychiatric and Neurodegenerative Disorders.
C. Zhang (2017)
Regulation and organization of adenylyl cyclases and cAMP.
D. M. Cooper (2003)
Forskolin as a Tool for Examining Adenylyl Cyclase Expression, Regulation, and G Protein Signaling
P. Insel (2004)
Compartmentation of cyclic nucleotide signaling in the heart: the role of cyclic nucleotide phosphodiesterases.
R. Fischmeister (2006)
Cholesterol depletion modulates basal L-type Ca2+ current and abolishes its -adrenergic enhancement in ventricular myocytes.
Hiroto Tsujikawa (2008)
Heterodimers of adenylyl cyclases 2 and 5 show enhanced functional responses in the presence of Galpha s.
A. Baragli (2008)
High Efficacy but Low Potency of δ-Opioid Receptor-G Protein Coupling in Brij-58-Treated, Low-Density Plasma Membrane Fragments
L. Roubalová (2015)
See more
Semantic Scholar Logo Some data provided by SemanticScholar