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A 2 Adrenergic Receptor Signaling Complex Assembled with the Ca2+ Channel Cav1.2
Monika A. Davare,1*Vladimir Avdonin,2Duane D. Hall,1Erik M. Peden,1Alain Burette,3Richard J. Weinberg,3Mary C. Horne,1Toshinori Hoshi,2Johannes W. Hell1*
The existence of a large number of receptors coupled to
heterotrimeric guanine nucleotide binding proteins (G proteins) raisesthe question of how a particular receptor selectively regulatesspecific targets. We provide insight into this question by identifyinga prototypical macromolecular signaling complex. The 2
adrenergicreceptor was found to be directly associated with one of its
ultimateeffectors, the class C L-type calcium channel
Cav1.2. This complexalso contained a G protein, an
adenylyl cyclase, cyclic adenosinemonophosphate-dependent protein
kinase, and the counterbalancingphosphatase PP2A. Our
electrophysiological recordings from hippocampalneurons demonstrate
highly localized signal transduction fromthe receptor to the channel.
The assembly of this signaling complexprovides a mechanism that
ensures specific and rapid signalingby a G protein-coupled
receptor.
1 Department of Pharmacology, University of
Wisconsin, Madison, WI 53706, USA.
2 Department of
Physiology and Biophysics, University of Iowa, Iowa City, IA 52242, USA.
3 Department of Cell Biology and Anatomy,
University of North Carolina, Chapel Hill, NC 27599, USA.
*
Present address: Vollum Institute, Oregon Health Sciences
University, Portland, OR 97201, USA.
Present address: Department of Pharmacology,
University of Iowa, Iowa, City, IA 52242, USA.
To whom correspondence should be addressed. E-mail:
johannes-hell{at}uiowa.edu
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2 Adrenergic Receptor Signaling Complex Assembled with the Ca2+ Channel Cav1.2
2
adrenergic receptor was found to be directly associated with one of its
ultimate effectors, the class C L-type calcium channel
Cav1.2. 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.