Abstract

We propose to use recombinant DNA techniques to further our studies of the expression, structure, and function of DARPP-32, ARPP-21, ARPP- 19, and ARPP- 16. We will characterize the rat cDNAs, which, when compared to the bovine sequences, will allow us to detect highly conserved regions of probable physiologic significance. These probes will also be used to study specific mRNA levels in pharmacologically manipulated rats. We will also characterize the human cDNAs for these proteins, and these probes will be utilized in studies of samples from patients with basal ganglia diseases, and in molecular genetic applications. We will isolate the mouse genomic clone for ARPP-19/16 for use in cell-expression studies, and to obtain a promotor region which will be used to direct expression in transgenic mice. These mice will be used for physiological and biochemical studies. Finally, the cDNAs will be used to produce mutagenized forms of the protein for biochemical studies.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Program Projects (P01)
Project #
2P01MH040899-06
Application #
3881244
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
6
Fiscal Year
1990
Total Cost
Indirect Cost

  Institution

Name
Rockefeller University
Department
Type
DUNS #
071037113
City
New York
State
NY
Country
United States
Zip Code
10065

  Publications

Plattner, Florian; Hayashi, Kanehiro; Hernández, Adan et al. (2015) The role of ventral striatal cAMP signaling in stress-induced behaviors. Nat Neurosci 18:1094-100
Kimura, Toru; Han, Wonsun; Pagel, Philipp et al. (2011) Protein phosphatase 2A interacts with the Na,K-ATPase and modulates its trafficking by inhibition of its association with arrestin. PLoS One 6:e29269
Zhou, Mingming; Rebholz, Heike; Brocia, Christine et al. (2010) Forebrain overexpression of CK1delta leads to down-regulation of dopamine receptors and altered locomotor activity reminiscent of ADHD. Proc Natl Acad Sci U S A 107:4401-6
Bertran-Gonzalez, Jesus; Håkansson, Kerstin; Borgkvist, Anders et al. (2009) Histone H3 phosphorylation is under the opposite tonic control of dopamine D2 and adenosine A2A receptors in striatopallidal neurons. Neuropsychopharmacology 34:1710-20
Kuroiwa, Mahomi; Bateup, Helen S; Shuto, Takahide et al. (2008) Regulation of DARPP-32 phosphorylation by three distinct dopamine D1-like receptor signaling pathways in the neostriatum. J Neurochem 107:1014-26
Nishi, Akinori; Kuroiwa, Mahomi; Miller, Diane B et al. (2008) Distinct roles of PDE4 and PDE10A in the regulation of cAMP/PKA signaling in the striatum. J Neurosci 28:10460-71
Barbano, Paolo E; Spivak, Marina; Flajolet, Marc et al. (2007) A mathematical tool for exploring the dynamics of biological networks. Proc Natl Acad Sci U S A 104:19169-74
Borgkvist, Anders; Usiello, Alessandro; Greengard, Paul et al. (2007) Activation of the cAMP/PKA/DARPP-32 signaling pathway is required for morphine psychomotor stimulation but not for morphine reward. Neuropsychopharmacology 32:1995-2003
Bullock, S Andrew; Platholi, Jimcy; Gjyrezi, Ada et al. (2007) Differential regulation of protein phosphatase-1(I) by neurabin. Biochem Biophys Res Commun 358:140-4
Svenningsson, Per; Bateup, Helen; Qi, Hongshi et al. (2007) Involvement of AMPA receptor phosphorylation in antidepressant actions with special reference to tianeptine. Eur J Neurosci 26:3509-17

Showing the most recent 10 out of 219 publications