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Neural Plasticity
Volume 2017, Article ID 4153076, 16 pages
https://doi.org/10.1155/2017/4153076
Research Article

Mechanisms and Consequences of Dopamine Depletion-Induced Attenuation of the Spinophilin/Neurofilament Medium Interaction

1Department of Biology, Indiana University-Purdue University Indianapolis, 723 W. Michigan St., Indianapolis, IN 46202, USA
2Department of Chemistry and Chemical Biology, Indiana University-Purdue University Indianapolis, 723 W. Michigan St., Indianapolis, IN 46202, USA
3Neuroscience Undergraduate Program, Indiana University-Purdue University Indianapolis, 723 W. Michigan St., Indianapolis, IN 46202, USA
4Department of Psychology, Indiana University-Purdue University Indianapolis, 723 W. Michigan St., Indianapolis, IN 46202, USA
5Molecular Physiology and Biophysics, Vanderbilt University School of Medicine University, 724 Robinson Research Building, 23rd Ave South at Pierce, Nashville, TN 37232, USA
6Department of Biochemistry and the Mass Spectrometry Research Center, Vanderbilt University School of Medicine University, 465 21st Ave S. Room 9160, MRB III, Nashville, TN 37232, USA
7Stark Neurosciences Research Institute, Indiana University School of Medicine, Indiana, IN, USA

Correspondence should be addressed to Anthony J. Baucum II; ude.iupui@mucuabja

Received 9 January 2017; Accepted 16 February 2017; Published 28 May 2017

Academic Editor: Tomasz Wójtowicz

Copyright © 2017 Andrew C. Hiday et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Signaling changes that occur in the striatum following the loss of dopamine neurons in the Parkinson disease (PD) are poorly understood. While increases in the activity of kinases and decreases in the activity of phosphatases have been observed, the specific consequences of these changes are less well understood. Phosphatases, such as protein phosphatase 1 (PP1), are highly promiscuous and obtain substrate selectivity via targeting proteins. Spinophilin is the major PP1-targeting protein enriched in the postsynaptic density of striatal dendritic spines. Spinophilin association with PP1 is increased concurrent with decreases in PP1 activity in an animal model of PD. Using proteomic-based approaches, we observed dopamine depletion-induced decreases in spinophilin binding to multiple protein classes in the striatum. Specifically, there was a decrease in the association of spinophilin with neurofilament medium (NF-M) in dopamine-depleted striatum. Using a heterologous cell line, we determined that spinophilin binding to NF-M required overexpression of the catalytic subunit of protein kinase A and was decreased by cyclin-dependent protein kinase 5. Functionally, we demonstrate that spinophilin can decrease NF-M phosphorylation. Our data determine mechanisms that regulate, and putative consequences of, pathological changes in the association of spinophilin with NF-M that are observed in animal models of PD.