Abstract

We propose to further characterize the properties of several previously described basal ganglia-enriched protein phosphorylation systems and phosphoprotein substrates for cAMP-dependent protein kinase. We will study the physiological and pharmacological regulation of the state of phosphorylation of phosphoproteins in intact cellular systems derived from basal ganglia structures. These include brain slices, synaptosomes, and dissociated striatal neurons. Both single and multiple interacting first messenger candidates (e.g.,dopamine and glutamate) will be examined in these systems. We will also study the levels of identified phosphoproteins following different pharmacological treatments which interfere with synaptic transmission in the basal ganglia and limbic regions. Finally, using electrophysiological methods, we will evaluate the physiological role of various components of the protein phosphorylation systems in the basal ganglia by direct intracellular injections of purified protein kinases, protein phosphatases, and phosphoproteins into isolated striatal neurons. The results are expected to increase our understanding of the mechanisms of signal transduction involved in normal and pathological conditions in the basal ganglia and associated limbic regions.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Program Projects (P01)
Project #
2P01MH040899-06
Application #
3881242
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