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.
Science Signaling

Site Tools

  • AAAS
  • Subscribe
  • Feedback

Site Search

Search Advanced

Logo for

Science 287 (5458): 1660-1664

Copyright © 2000 by the American Association for the Advancement of Science

Dual Signaling Regulated by Calcyon, a D1 Dopamine Receptor Interacting Protein

Nelson Lezcano, 1 Ladislav Mrzljak, 2 Steven Eubanks, 1 Robert Levenson, 3 Patricia Goldman-Rakic, 2 Clare Bergson 1*

The synergistic response of cells to the stimulation of multiple receptors has been ascribed to receptor cross talk; however, the specific molecules that mediate the resultant signal amplification have not been defined. Here a 24-kilodalton single transmembrane protein, designated calcyon, we functionally characterize that interacts with the D1 dopamine receptor. Calcyon localizes to dendritic spines of D1 receptor-expressing pyramidal cells in prefrontal cortex. These studies delineate a mechanism of Gq- and Gs-coupled heterotrimeric GTP-binding protein-coupled receptor cross talk by which D1 receptors can shift effector coupling to stimulate robust intracellular calcium (Ca2+i) release as a result of interaction with calcyon. The role of calcyon in potentiating Ca2+-dependent signaling should provide insight into the D1 receptor-modulated cognitive functions of prefrontal cortex.

1 Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta, GA 30912-2300, USA.
2 Section of Neurobiology, Yale School of Medicine, New Haven, CT 06510, USA.
3 Department of Pharmacology, Pennsylvania State College of Medicine, Hershey, PA 17033, USA.
*   To whom correspondence should be addressed. E-mail: cbergson{at}mail.mcg.edu

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
A novel, conformation-specific allosteric inhibitor of the tachykinin NK2 receptor (NK2R) with functionally selective properties.
E. L. Maillet, N. Pellegrini, C. Valant, B. Bucher, M. Hibert, J.-J. Bourguignon, and J.-L. Galzi (2007)
FASEB J 21, 2124-2134
   Abstract »    Full Text »    PDF »
Inhibition of the Dopamine D1 Receptor Signaling by PSD-95.
J. Zhang, A. Vinuela, M. H. Neely, P. J. Hallett, S. G. N. Grant, G. M. Miller, O. Isacson, M. G. Caron, and W.-D. Yao (2007)
J. Biol. Chem. 282, 15778-15789
   Abstract »    Full Text »    PDF »
D1-like dopamine receptors selectively block P/Q-type calcium channels to reduce glutamate release onto cholinergic basal forebrain neurones of immature rats.
T. Momiyama and Y. Fukazawa (2007)
J. Physiol. 580, 103-117
   Abstract »    Full Text »    PDF »
Calcyon, a Novel Partner of Clathrin Light Chain, Stimulates Clathrin-mediated Endocytosis.
J. Xiao, R. Dai, L. Negyessy, and C. Bergson (2006)
J. Biol. Chem. 281, 15182-15193
   Abstract »    Full Text »    PDF »
Dopaminergic Abnormalities in Select Thalamic Nuclei in Schizophrenia: Involvement of the Intracellular Signal Integrating Proteins Calcyon and Spinophilin.
S. M. Clinton, H. M. Ibrahim, K. A. Frey, K. L. Davis, V. Haroutunian, and J. H. Meador-Woodruff (2005)
Am J Psychiatry 162, 1859-1871
   Abstract »    Full Text »    PDF »
Metabotropic Glutamate Receptors and Dopamine Receptors Cooperate to Enhance Extracellular Signal-Regulated Kinase Phosphorylation in Striatal Neurons.
P. J. Voulalas, L. Holtzclaw, J. Wolstenholme, J. T. Russell, and S. E. Hyman (2005)
J. Neurosci. 25, 3763-3773
   Abstract »    Full Text »    PDF »
Gq/11-Induced and Spontaneous Waves of Coordinated Network Activation in Developing Frontal Cortex.
D. P. Calderon, N. Leverkova, and A. Peinado (2005)
J. Neurosci. 25, 1737-1749
   Abstract »    Full Text »    PDF »
G protein-coupled receptors show unusual patterns of intrinsic unfolding.
V.-P. Jaakola, J. Prilusky, J. L. Sussman, and A. Goldman (2005)
Protein Eng. Des. Sel. 18, 103-110
   Abstract »    Full Text »    PDF »
D1 Dopamine Receptor Regulation of the Levels of the Cell-cycle-controlling Proteins, Cyclin D, P27 and Raf-1, in Cerebral Cortical Precursor Cells is Mediated Through cAMP-independent Pathways.
L. Zhang, J. Bai, A. S. Undie, C. Bergson, and M. S. Lidow (2005)
Cereb Cortex 15, 74-84
   Abstract »    Full Text »    PDF »
A Library of 7TM Receptor C-terminal Tails: INTERACTIONS WITH THE PROPOSED POST-ENDOCYTIC SORTING PROTEINS ERM-BINDING PHOSPHOPROTEIN 50 (EBP50), N-ETHYLMALEIMIDE-SENSITIVE FACTOR (NSF), SORTING NEXIN 1 (SNX1), AND G PROTEIN-COUPLED RECEPTOR-ASSOCIATED SORTING PROTEIN (GASP).
A. Heydorn, B. P. Sondergaard, B. Ersboll, B. Holst, F. C. Nielsen, C. R. Haft, J. Whistler, and T. W. Schwartz (2004)
J. Biol. Chem. 279, 54291-54303
   Abstract »    Full Text »    PDF »
Functional genomics of the dopaminergic system in hypertension.
C. Zeng, H. Sanada, H. Watanabe, G. M. Eisner, R. A. Felder, and P. A. Jose (2004)
Physiol Genomics 19, 233-246
   Abstract »    Full Text »    PDF »
Identification of Tissue-Restricted Transcripts in Human Islets.
A. Maffei, Z. Liu, P. Witkowski, F. Moschella, G. D. Pozzo, E. Liu, K. Herold, R. J. Winchester, M. A. Hardy, and P. E. Harris (2004)
Endocrinology 145, 4513-4521
   Abstract »    Full Text »    PDF »
Dopamine Receptor-mediated Ca2+ Signaling in Striatal Medium Spiny Neurons.
T.-S. Tang and I. Bezprozvanny (2004)
J. Biol. Chem. 279, 42082-42094
   Abstract »    Full Text »    PDF »
Dopamine D1 and D2 Receptor Co-activation Generates a Novel Phospholipase C-mediated Calcium Signal.
S. P. Lee, C. H. So, A. J. Rashid, G. Varghese, R. Cheng, A. J. Lanca, B. F. O'Dowd, and S. R. George (2004)
J. Biol. Chem. 279, 35671-35678
   Abstract »    Full Text »    PDF »
Regulations of Methamphetamine Reward by Extracellular Signal-Regulated Kinase 1/2/ets-Like Gene-1 Signaling Pathway via the Activation of Dopamine Receptors.
H. Mizoguchi, K. Yamada, M. Mizuno, T. Mizuno, A. Nitta, Y. Noda, and T. Nabeshima (2004)
Mol. Pharmacol. 65, 1293-1301
   Abstract »    Full Text »
Enhancement of Working Memory in Aged Monkeys by a Sensitizing Regimen of Dopamine D1 Receptor Stimulation.
S. A. Castner and P. S. Goldman-Rakic (2004)
J. Neurosci. 24, 1446-1450
   Abstract »    Full Text »    PDF »
Dopamine D1/D5 Receptor Modulates State-Dependent Switching of Soma-Dendritic Ca2+ Potentials via Differential Protein Kinase A and C Activation in Rat Prefrontal Cortical Neurons.
C. E. Young and C. R. Yang (2004)
J. Neurosci. 24, 8-23
   Abstract »    Full Text »    PDF »
Protein phosphatase 2C binds selectively to and dephosphorylates metabotropic glutamate receptor 3.
M. Flajolet, S. Rakhilin, H. Wang, N. Starkova, N. Nuangchamnong, A. C. Nairn, and P. Greengard (2003)
PNAS 100, 16006-16011
   Abstract »    Full Text »    PDF »
Elevated Intracellular Calcium Triggers Recruitment of the Receptor Cross-talk Accessory Protein Calcyon to the Plasma Membrane.
M. K. Ali and C. Bergson (2003)
J. Biol. Chem. 278, 51654-51663
   Abstract »    Full Text »    PDF »
Molecular Mechanisms and Therapeutical Implications of Intramembrane Receptor/Receptor Interactions among Heptahelical Receptors with Examples from the Striatopallidal GABA Neurons.
L. F. Agnati, S. Ferre, C. Lluis, R. Franco, and K. Fuxe (2003)
Pharmacol. Rev. 55, 509-550
   Abstract »    Full Text »    PDF »
Up-regulation of the D1 Dopamine Receptor-Interacting Protein, Calcyon, in Patients With Schizophrenia.
P. O. Koh, C. Bergson, A. S. Undie, P. S. Goldman-Rakic, and M. S. Lidow (2003)
Arch Gen Psychiatry 60, 311-319
   Abstract »    Full Text »    PDF »
Up-regulation of the D1 Dopamine Receptor-Interacting Protein, Calcyon, in Patients With Schizophrenia.
P. O. Koh, C. Bergson, A. S. Undie, P. S. Goldman-Rakic, and M. S. Lidow (2003)
Arch Gen Psychiatry 60, 311-319
   Abstract »    Full Text »
G{alpha}12- and G{alpha}13-Protein Subunit Linkage of D5 Dopamine Receptors in the Nephron.
S. Zheng, P. Yu, C. Zeng, Z. Wang, Z. Yang, P. M. Andrews, R. A. Felder, and P. A. Jose (2003)
Hypertension 41, 604-610
   Abstract »    Full Text »    PDF »
Dopamine Enhances EPSCs in Layer II-III Pyramidal Neurons in Rat Prefrontal Cortex.
C. Gonzalez-Islas and J. J. Hablitz (2003)
J. Neurosci. 23, 867-875
   Abstract »    Full Text »    PDF »
Up-regulation of neuronal calcium sensor-1 (NCS-1) in the prefrontal cortex of schizophrenic and bipolar patients.
P. O. Koh, A. S. Undie, N. Kabbani, R. Levenson, P. S. Goldman-Rakic, and M. S. Lidow (2003)
PNAS 100, 313-317
   Abstract »    Full Text »    PDF »
Mutations in the Extracellular Amino-terminal Domain of the NK2 Neurokinin Receptor Abolish cAMP Signaling but Preserve Intracellular Calcium Responses.
S. Lecat, B. Bucher, Y. Mely, and J.-L. Galzi (2002)
J. Biol. Chem. 277, 42034-42048
   Abstract »    Full Text »    PDF »
D2 and D3 Dopamine Receptor Cell Surface Localization Mediated by Interaction with Protein 4.1N.
A. V. Binda, N. Kabbani, R. Lin, and R. Levenson (2002)
Mol. Pharmacol. 62, 507-513
   Abstract »    Full Text »    PDF »
Cross signaling, cell specificity, and physiology.
J. E. Dumont, S. Dremier, I. Pirson, and C. Maenhaut (2002)
Am J Physiol Cell Physiol 283, C2-C28
   Abstract »    Full Text »    PDF »
Modulation of receptor cycling by neuron-enriched endosomal protein of 21 kD.
P. Steiner, J.-C. F. Sarria, L. Glauser, S. Magnin, S. Catsicas, and H. Hirling (2002)
J. Cell Biol. 157, 1197-1209
   Abstract »    Full Text »    PDF »
G Protein-Coupled Receptor Allosterism and Complexing.
A. Christopoulos and T. Kenakin (2002)
Pharmacol. Rev. 54, 323-374
   Abstract »    Full Text »    PDF »
D1/D5 Dopamine Receptors Stimulate Intracellular Calcium Release in Primary Cultures of Neocortical and Hippocampal Neurons.
N. Lezcano and C. Bergson (2002)
J Neurophysiol 87, 2167-2175
   Abstract »    Full Text »    PDF »
Functional Expression of Heteromeric Calcitonin Gene-related Peptide and Adrenomedullin Receptors in Yeast.
J. J. Miret, L. Rakhilina, L. Silverman, and B. Oehlen (2002)
J. Biol. Chem. 277, 6881-6887
   Abstract »    Full Text »    PDF »
D1 dopamine receptor regulation of NHE3 during development in spontaneously hypertensive rats.
X. X. Li, J. Xu, S. Zheng, F. E. Albrecht, J. E. Robillard, G. M. Eisner, and P. A. Jose (2001)
Am J Physiol Regulatory Integrative Comp Physiol 280, R1650-R1656
   Abstract »    Full Text »    PDF »
Regulation of neuroblast mitosis is determined by PACAP receptor isoform expression.
A. Nicot and E. DiCicco-Bloom (2001)
PNAS 98, 4758-4763
   Abstract »    Full Text »    PDF »
Evolving Concepts in G Protein-Coupled Receptor Endocytosis: The Role in Receptor Desensitization and Signaling.
S. S. G. Ferguson (2001)
Pharmacol. Rev. 53, 1-24
   Abstract »    Full Text »    PDF »
Involvement of the Extracellular Signal-Regulated Kinase Cascade for Cocaine-Rewarding Properties.
E. Valjent, J.-C. Corvol, C. Pages, M.-J. Besson, R. Maldonado, and J. Caboche (2000)
J. Neurosci. 20, 8701-8709
   Abstract »    Full Text »    PDF »
Agonist-regulated Interaction between alpha 2-Adrenergic Receptors and Spinophilin.
J. G. Richman, A. E. Brady, Q. Wang, J. L. Hensel, R. J. Colbran, and L. E. Limbird (2001)
J. Biol. Chem. 276, 15003-15008
   Abstract »    Full Text »    PDF »

ADVERTISEMENT
Click Me!

ADVERTISEMENT

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (pre-2008: Science's STKE. ISSN 1525-8882)