A β ₂ Adrenergic Receptor Signaling Complex Assembled with the Ca ²⁺ Channel Ca _v 1.2

TLDR

The existence of many G protein‑coupled receptors raises the question of how a specific receptor selectively regulates its targets. We address this by identifying a prototypical macromolecular signaling complex. The complex contains a G protein, adenylyl cyclase, cAMP‑dependent protein kinase, and phosphatase PP2A. The β2 adrenergic receptor directly associates with the Ca(v)1.2 channel, and electrophysiological recordings in hippocampal neurons show highly localized signal transduction, demonstrating that this complex enables specific and rapid G protein‑coupled receptor signaling.

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.