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Cell-Type-Specific Proteomics: A Neuroscience Perspective
Correction published on 13 February 2019, see Proteomes 2019, 7(1), 7.
Open AccessArticle

Proteomic Analysis of the Spinophilin Interactome in Rodent Striatum Following Psychostimulant Sensitization

1
Stark Neurosciences Research Institute, Indiana University School of Medicine Medical Neuroscience Graduate Program, Indianapolis, IN 46278, USA
2
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46278, USA
3
Department of Biology, Ball State University, Muncie, IN 47306, USA
4
Department of Biology, Indiana University-Purdue University Indianapolis, Indianapolis, IN 46202, USA
5
Stark Neurosciences Research Institute Indianapolis, Indianapolis, IN 46202, USA
6
Department of Pharmacology and Toxicology, Indiana University School of Medicine, Indianapolis, IN 46202, USA
*
Author to whom correspondence should be addressed.
Proteomes 2018, 6(4), 53; https://doi.org/10.3390/proteomes6040053
Received: 12 October 2018 / Revised: 10 December 2018 / Accepted: 13 December 2018 / Published: 17 December 2018
(This article belongs to the Special Issue Neuroproteomics)
Glutamatergic projections from the cortex and dopaminergic projections from the substantia nigra or ventral tegmental area synapse on dendritic spines of specific GABAergic medium spiny neurons (MSNs) in the striatum. Direct pathway MSNs (dMSNs) are positively coupled to protein kinase A (PKA) signaling and activation of these neurons enhance specific motor programs whereas indirect pathway MSNs (iMSNs) are negatively coupled to PKA and inhibit competing motor programs. An imbalance in the activity of these two programs is observed following increased dopamine signaling associated with exposure to psychostimulant drugs of abuse. Alterations in MSN signaling are mediated by changes in MSN protein post-translational modifications, including phosphorylation. Whereas direct changes in specific kinases, such as PKA, regulate different effects observed in the two MSN populations, alterations in the specific activity of serine/threonine phosphatases, such as protein phosphatase 1 (PP1) are less well known. This lack of knowledge is due, in part, to unknown, cell-specific changes in PP1 targeting proteins. Spinophilin is the major PP1-targeting protein in striatal postsynaptic densities. Using proteomics and immunoblotting approaches along with a novel transgenic mouse expressing hemagglutainin (HA)-tagged spinophilin in dMSNs and iMSNs, we have uncovered cell-specific regulation of the spinophilin interactome following a sensitizing regimen of amphetamine. These data suggest regulation of spinophilin interactions in specific MSN cell types and may give novel insight into putative cell-specific, phosphatase-dependent signaling pathways associated with psychostimulants. View Full-Text
Keywords: amphetamine; spinophilin; protein phosphatase-1; dopamine; striatum amphetamine; spinophilin; protein phosphatase-1; dopamine; striatum
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MDPI and ACS Style

Watkins, D.S.; True, J.D.; Mosley, A.L.; Baucum, A.J., II. Proteomic Analysis of the Spinophilin Interactome in Rodent Striatum Following Psychostimulant Sensitization. Proteomes 2018, 6, 53.

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