Signaling Complexes Tuning in to the Right Channel

Clustering of signaling proteins in highly ordered complexes continues to be major theme in studies of signal transduction. Davare et al. report that L-type Ca²⁺ channels from rat neurons are tightly linked to the β₂-adrenergic receptors (β₂ARs) that control channel conductance. The authors characterized a signaling complex that contains all of the intermediates for signaling from the receptor to the channel: the β₂AR itself, the heterotrimeric guanine nucleotide binding protien Gα_s, the adenylyl cyclase activated by the G protein to produce cyclic adenosine monophosphate (cAMP), and the cAMP-dependent protein kinase, which controls the channel through covalent phosphorylation. This close association appears to restrict signaling by β₂AR to those channels that are in the receptor complex. Patch-clamp recordings from a tiny portion of the cell membrane showed that local application of an agonist (within the pipette) could activate the calcium channel, but that the application of the same stimulus to the rest of the cell did not activate the channels within the patch. Laporte et al. wrote an accompanying Perspective on the Davare et al. article.

M. A. Davare, V. Avdonin, D. D. Hall, E. M. Peden, A. Burette, R. J. Weinberg, M. C. Horne, T. Hoshi, J. W. Hell, A β₂ adrenergic receptor signaling complex assembled with the Ca²⁺ channel Ca_v1.2. Science 293, 98-101 (2001). [Abstract] [Full Text]

S. A. Laporte, R. H. Oakley, M. G. Caron, Bringing channels closer to the action! Science 293, 62-63 (2001). [Full Text]