HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 275, Issue 42, 32672-32680, October 20, 2000

This Article Full Text Full Text (PDF) All Versions of this Article: 275/42/32672    most recent M002780200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bofill-Cardona, E. Articles by Nanoff, C. Search for Related Content PubMed PubMed Citation Articles by Bofill-Cardona, E. Articles by Nanoff, C. Social Bookmarking                      What's this?

Binding of Calmodulin to the D₂-Dopamine Receptor Reduces Receptor Signaling by Arresting the G Protein Activation Switch^*

Elisa Bofill-Cardona, Oliver Kudlacek, Qiong Yang, Horst Ahorn^§, Michael Freissmuth, and Christian Nanoff^¶

From the  Institute of Pharmacology, University of Vienna, Währinger Strasse 13a, A-1090 Vienna and ^§ Boehringer Ingelheim Austria GmbH, Dr.-Boehringer-Gasse 5, A-1120 Vienna, Austria

Signaling by D₂-dopamine receptors in neurons likely proceeds in the presence of Ca²⁺ oscillations. We describe here the biochemical basis for a cross-talk between intracellular Ca²⁺ and the D₂ receptor. By activation of calmodulin (CaM), Ca²⁺ directly inhibits the D₂ receptor; this conclusion is based on the following observations: (i) The receptor contains a CaM-binding motif in the NH₂-terminal end of the third loop, a domain involved in activating G_i/o. A peptide fragment encompassing this domain (D2N) bound dansylated CaM in a Ca²⁺-dependent manner (K_D ~ 0.1 µM). (ii) Activation of purified G_i1 by D2N, and D₂ receptor-promoted GTPS (guanosine 5'-(3-O-thio)triphosphate) binding in membranes was suppressed by Ca²⁺/CaM (IC₅₀ ~ 0.1 µM). (iii) If Ca²⁺ influx was elicited in D₂ receptor-expressing HEK293 cells, agonist-dependent inhibition of cAMP formation decreased. This effect was not seen with other G_i-coupled receptors (A₁-adenosine and Mel_1A-melatonin receptor). (iv) The D₂ receptor was retained by immobilized CaM and radiolabeled CaM was co-immunoprecipitated with the receptor. Specifically, inhibition by CaM does not result from uncoupling the D₂ receptor from its cognate G protein(s); rather, CaM directly targets the D₂ receptor to block the receptor-operated G protein activation switch.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				M. Labasque, E. Reiter, C. Becamel, J. Bockaert, and P. Marin Physical Interaction of Calmodulin with the 5-Hydroxytryptamine2C Receptor C-Terminus Is Essential for G Protein-independent, Arrestin-dependent Receptor Signaling Mol. Biol. Cell, November 1, 2008; 19(11): 4640 - 4650. [Abstract] [Full Text] [PDF]

				J. H. Lee, J. Lee, K. Y. Choi, R. Hepp, J.-Y. Lee, M. K. Lim, M. Chatani-Hinze, P. A. Roche, D. G. Kim, Y. S. Ahn, et al. Calmodulin dynamically regulates the trafficking of the metabotropic glutamate receptor mGluR5 PNAS, August 26, 2008; 105(34): 12575 - 12580. [Abstract] [Full Text] [PDF]

				Y. Liu, D. C. Buck, and K. A. Neve Novel Interaction of the Dopamine D2 Receptor and the Ca2+ Binding Protein S100B: Role in D2 Receptor Function Mol. Pharmacol., August 1, 2008; 74(2): 371 - 378. [Abstract] [Full Text] [PDF]

				M. J. Beckstead and J. T. Williams Long-Term Depression of a Dopamine IPSC J. Neurosci., February 21, 2007; 27(8): 2074 - 2080. [Abstract] [Full Text] [PDF]

				C. Nanoff, R. Koppensteiner, Q. Yang, E. Fuerst, H. Ahorn, and M. Freissmuth The Carboxyl Terminus of the G{alpha}-Subunit Is the Latch for Triggered Activation of Heterotrimeric G Proteins Mol. Pharmacol., January 1, 2006; 69(1): 397 - 405. [Abstract] [Full Text] [PDF]

				J. H. Turner and J. R. Raymond Interaction of Calmodulin with the Serotonin 5-Hydroxytryptamine2A Receptor: A PUTATIVE REGULATOR OF G PROTEIN COUPLING AND RECEPTOR PHOSPHORYLATION BY PROTEIN KINASE C J. Biol. Chem., September 2, 2005; 280(35): 30741 - 30750. [Abstract] [Full Text] [PDF]

				M. M. Belcheva, A. L. Clark, P. D. Haas, J. S. Serna, J. W. Hahn, A. Kiss, and C. J. Coscia {micro} and {kappa} Opioid Receptors Activate ERK/MAPK via Different Protein Kinase C Isoforms and Secondary Messengers in Astrocytes J. Biol. Chem., July 29, 2005; 280(30): 27662 - 27669. [Abstract] [Full Text] [PDF]

				H. H. Nickols, V. N. Shah, W. J. Chazin, and L. E. Limbird Calmodulin Interacts with the V2 Vasopressin Receptor: ELIMINATION OF BINDING TO THE C TERMINUS ALSO ELIMINATES ARGININE VASOPRESSIN-STIMULATED ELEVATION OF INTRACELLULAR CALCIUM J. Biol. Chem., November 5, 2004; 279(45): 46969 - 46980. [Abstract] [Full Text] [PDF]

				J. H. Turner, A. K. Gelasco, and J. R. Raymond Calmodulin Interacts with the Third Intracellular Loop of the Serotonin 5-Hydroxytryptamine1A Receptor at Two Distinct Sites: PUTATIVE ROLE IN RECEPTOR PHOSPHORYLATION BY PROTEIN KINASE C J. Biol. Chem., April 23, 2004; 279(17): 17027 - 17037. [Abstract] [Full Text] [PDF]

				H. Pankevych, V. Korkhov, M. Freissmuth, and C. Nanoff Truncation of the A1 Adenosine Receptor Reveals Distinct Roles of the Membrane-proximal Carboxyl Terminus in Receptor Folding and G Protein Coupling J. Biol. Chem., August 8, 2003; 278(32): 30283 - 30293. [Abstract] [Full Text] [PDF]

				J. Martinez, I. Moeller, H. Erdjument-Bromage, P. Tempst, and B. Lauring Parkinson's Disease-associated alpha -Synuclein Is a Calmodulin Substrate J. Biol. Chem., May 2, 2003; 278(19): 17379 - 17387. [Abstract] [Full Text] [PDF]

				S. Glaser, D. Alvaro, T. Roskams, J. L. Phinizy, G. Stoica, H. Francis, Y. Ueno, B. Barbaro, M. Marzioni, J. Mauldin, et al. Dopaminergic inhibition of secretin-stimulated choleresis by increased PKC-gamma expression and decrease of PKA activity Am J Physiol Gastrointest Liver Physiol, April 1, 2003; 284(4): G683 - G694. [Abstract] [Full Text] [PDF]

				N. Kabbani, L. Negyessy, R. Lin, P. Goldman-Rakic, and R. Levenson Interaction with Neuronal Calcium Sensor NCS-1 Mediates Desensitization of the D2 Dopamine Receptor J. Neurosci., October 1, 2002; 22(19): 8476 - 8486. [Abstract] [Full Text] [PDF]

				A. V. Binda, N. Kabbani, R. Lin, and R. Levenson D2 and D3 Dopamine Receptor Cell Surface Localization Mediated by Interaction with Protein 4.1N Mol. Pharmacol., September 1, 2002; 62(3): 507 - 513. [Abstract] [Full Text] [PDF]

				M. C. Kim, S. H. Lee, J. K. Kim, H. J. Chun, M. S. Choi, W. S. Chung, B. C. Moon, C. H. Kang, C. Y. Park, J. H. Yoo, et al. Mlo, a Modulator of Plant Defense and Cell Death, Is a Novel Calmodulin-binding Protein. ISOLATION AND CHARACTERIZATION OF A RICE Mlo HOMOLOGUE J. Biol. Chem., May 24, 2002; 277(22): 19304 - 19314. [Abstract] [Full Text] [PDF]

				M. M. Belcheva, M. Szucs, D. Wang, W. Sadee, and C. J. Coscia {micro}-Opioid Receptor-mediated ERK Activation Involves Calmodulin-dependent Epidermal Growth Factor Receptor Transactivation J. Biol. Chem., August 31, 2001; 276(36): 33847 - 33853. [Abstract] [Full Text] [PDF]

				O. El Far, E. Bofill-Cardona, J. M. Airas, V. O'Connor, S. Boehm, M. Freissmuth, C. Nanoff, and H. Betz Mapping of Calmodulin and Gbeta gamma Binding Domains within the C-terminal Region of the Metabotropic Glutamate Receptor 7A J. Biol. Chem., August 10, 2001; 276(33): 30662 - 30669. [Abstract] [Full Text] [PDF]