Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Sci. STKE, 24 October 2000
Vol. 2000, Issue 55, p. tw7
[DOI: 10.1126/stke.2000.55.tw7]

EDITORS' CHOICE

Neurobiology Calmodulin Reduces G protein Activation

The dopamine D2 receptor activates inhibitory G proteins that inhibit adenylyl cyclase activity, culminating in reduced production of cAMP. Ca2+ pathways can regulate effectors that are controlled by D2 receptors; however, the molecular interactions between these two paths are unclear. Bofill-Cardona et al. provide evidence that calmodulin (CaM) directly attenuates D2 receptor activation of the inhibitory G protein Gαi1. In the presence of calcimycin, a Ca2+ ionophore, the inhibitory effect of D2 receptor agonists on production of cAMP was reduced. CaM reduced guanosine 5'-O-(3'-thiotriphosphate) (GTP-{gamma}-S) loading in membranes containing D2 receptors and G proteins; however, this effect was not direct, because coincubation of CaM with Gαi1 and GTP-{gamma}-S did not alter the rate of GTP-{gamma}-S loading, and CaM did not directly bind Gαi1. The authors identified a cytoplasmic sequence in the D2 receptor, termed D2N, that bound CaM and Gαi1 simultaneously. D2N was required for the activation of Gαi1, but the presence of CaM inhibited G protein activation. Thus, these results suggest that CaM blocks the nucleotide exchange reaction on Gαi1 not by uncoupling D2 from Gαi1, but by preventing D2N-mediated enabling of the G protein activation switch.

Bofill-Cardona, E., Kudlacek, O., Yang, Q., Ahorn, H., Freissmuth, M., and Nanoff, C. (2000) Binding of calmodulin to the D2-dopamine receptor reduces receptor signaling by arresting the G protein activation switch. J. Biol. Chem. 275: 32672-32680. [Abstract] [Full Text]

Citation: Calmodulin Reduces G protein Activation. Sci. STKE 2000, tw7 (2000).


To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882