This is the second competing renewal of our Program Project Grant, """"""""Drugs of Abuse: Role of Protein phosphorylation"""""""" (DA 10044), which was initially funded in 1996 and again in 2001. The grant has been highly successful based on research productivity and initiation of new research projects. The overall objective of the Program Project Grant remains the same as the original, namely, to elucidate the molecular basis of the actions of drugs of abuse, particularly psychostimulants, in the dorsal striatum and nucleus accumbens. The addictive properties of drugs of abuse such as psychostimulants depend on their ability to augment dopamine neurotransmission in the basal ganglia. The Program Project Grant is organized in four Projects, a Scientific Core and an Administrative Core. The Administrative Core staff will support the integration of the researchers and institutions involved in the Program Project Grant. The main goal of the Scientific Core is to provide a research and technical support facility for all of the Program projects. Responsibilities of the Scientific Core will include the creation, characterization, and breeding of genetically altered animals;the design and execution of yeast two-hybrid studies;the production and maintenance of key reagents stocks and new reagents; and the performance of certain routine tasks required to accomplish the studies described in Projects IIV. Project I, """"""""Psychostimulants and Dendritic spines,"""""""" will focus on the role five regulators of actin dynamics play as targets of psychostimulants in the dendritic spines. Project II, """"""""The Role of DARPP- 32, CK1, and CK2 in Mediating the Molecular and Behavioral Effects of Drugs of Abuse,"""""""" will extend previous studies of four key phosphorylation sites of DARPP-32 upon in vivo administration of drugs of abuse and chronic exposure to drugs of abuse. Project III, """"""""Striatal Phosphoproteins and the Actions of Psychostimulants,"""""""" which will be a subcontract carried out at Yale University School of Medicine, study the role(s) of RCS and ARPP-16 in mediating or modulating the actions of psychostimulants as well as study the roles of the three isoforms of PP1 (PPl∀, ∃and ) in the actions of psychostimulants. Project IV, """"""""The Role of GPCR-interacting Proteins in the Actions of Pscyhostimulants,"""""""" will utilize yeast twohybrid screening to further investigate the multiple intracellular signaling pathways of GPCR and its protein-interacting subunits in mediating actions of cocaine, D-amphetamine, ecstasy and caffeine.

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Research Program Projects (P01)
Project #
Application #
Study Section
Special Emphasis Panel (ZDA1-RXL-E (18))
Program Officer
Satterlee, John S
Project Start
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Rockefeller University
Other Basic Sciences
Other Domestic Higher Education
New York
United States
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Li, Daniel; Musante, Veronica; Zhou, Wenliang et al. (2018) Striatin-1 is a B subunit of protein phosphatase PP2A that regulates dendritic arborization and spine development in striatal neurons. J Biol Chem 293:11179-11194
Seo, J-S; Zhong, P; Liu, A et al. (2018) Elevation of p11 in lateral habenula mediates depression-like behavior. Mol Psychiatry 23:1113-1119
Madero-Pérez, Jesús; Fdez, Elena; Fernández, Belén et al. (2018) Parkinson disease-associated mutations in LRRK2 cause centrosomal defects via Rab8a phosphorylation. Mol Neurodegener 13:3
Chang, Audrey N; Gao, Ning; Liu, Zhenan et al. (2018) The dominant protein phosphatase PP1c isoform in smooth muscle cells, PP1c?, is essential for smooth muscle contraction. J Biol Chem 293:16677-16686
Musante, Veronica; Li, Lu; Kanyo, Jean et al. (2017) Reciprocal regulation of ARPP-16 by PKA and MAST3 kinases provides a cAMP-regulated switch in protein phosphatase 2A inhibition. Elife 6:
Milosevic, Ana; Liebmann, Thomas; Knudsen, Margarete et al. (2017) Cell- and region-specific expression of depression-related protein p11 (S100a10) in the brain. J Comp Neurol 525:955-975
Ceglia, Ilaria; Lee, Ko-Woon; Cahill, Michael E et al. (2017) WAVE1 in neurons expressing the D1 dopamine receptor regulates cellular and behavioral actions of cocaine. Proc Natl Acad Sci U S A 114:1395-1400
Seo, J-S; Wei, J; Qin, L et al. (2017) Cellular and molecular basis for stress-induced depression. Mol Psychiatry 22:1440-1447
Nishi, Akinori; Matamales, Miriam; Musante, Veronica et al. (2017) Glutamate Counteracts Dopamine/PKA Signaling via Dephosphorylation of DARPP-32 Ser-97 and Alteration of Its Cytonuclear Distribution. J Biol Chem 292:1462-1476
Andrade, Erika C; Musante, Veronica; Horiuchi, Atsuko et al. (2017) ARPP-16 Is a Striatal-Enriched Inhibitor of Protein Phosphatase 2A Regulated by Microtubule-Associated Serine/Threonine Kinase 3 (Mast 3 Kinase). J Neurosci 37:2709-2722

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