Abstract
The existence of a large number of receptors coupled to heterotrimeric guanine nucleotide binding proteins (G proteins) raises the question of how a particular receptor selectively regulates specific targets. We provide insight into this question by identifying a prototypical macromolecular signaling complex. The beta(2) adrenergic receptor was found to be directly associated with one of its ultimate effectors, the class C L-type calcium channel Ca(v)1.2. This complex also contained a G protein, an adenylyl cyclase, cyclic adenosine monophosphate-dependent protein kinase, and the counterbalancing phosphatase PP2A. Our electrophysiological recordings from hippocampal neurons demonstrate highly localized signal transduction from the receptor to the channel. The assembly of this signaling complex provides a mechanism that ensures specific and rapid signaling by a G protein-coupled receptor.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adenylyl Cyclases / metabolism
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Adrenergic beta-2 Receptor Agonists
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Albuterol / pharmacology
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Animals
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Calcium Channels, L-Type / genetics
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Calcium Channels, L-Type / metabolism*
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Cell Line
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Cell Membrane / metabolism
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Cyclic AMP-Dependent Protein Kinases / metabolism
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Electric Conductivity
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Fluorescent Antibody Technique
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Heterotrimeric GTP-Binding Proteins / metabolism
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Humans
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Isoproterenol / pharmacology
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Kinetics
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Macromolecular Substances
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Neurons / cytology
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Neurons / drug effects
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Neurons / enzymology
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Neurons / metabolism
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Phosphoprotein Phosphatases / metabolism
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Precipitin Tests
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Prosencephalon / cytology
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Prosencephalon / metabolism
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Protein Binding
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Pyramidal Cells / cytology
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Pyramidal Cells / drug effects
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Pyramidal Cells / enzymology
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Pyramidal Cells / metabolism
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Rats
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Receptors, Adrenergic, beta-2 / genetics
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Receptors, Adrenergic, beta-2 / metabolism*
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Signal Transduction*
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Substrate Specificity
Substances
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Adrenergic beta-2 Receptor Agonists
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Calcium Channels, L-Type
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L-type calcium channel alpha(1C)
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Macromolecular Substances
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Receptors, Adrenergic, beta-2
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Cyclic AMP-Dependent Protein Kinases
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Phosphoprotein Phosphatases
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Heterotrimeric GTP-Binding Proteins
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Adenylyl Cyclases
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Isoproterenol
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Albuterol