Mechanisms and Consequences of Dopamine Depletion-Induced Attenuation of the Spinophilin/Neurofilament Medium Interaction
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 we...
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| Format: | Article |
| Language: | English |
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Wiley
2017-01-01
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| Series: | Neural Plasticity |
| Online Access: | http://dx.doi.org/10.1155/2017/4153076 |
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| author | Andrew C. Hiday Michael C. Edler Asma B. Salek Cameron W. Morris Morrent Thang Tyler J. Rentz Kristie L. Rose Lisa M. Jones Anthony J. Baucum |
| author_facet | Andrew C. Hiday Michael C. Edler Asma B. Salek Cameron W. Morris Morrent Thang Tyler J. Rentz Kristie L. Rose Lisa M. Jones Anthony J. Baucum |
| author_sort | Andrew C. Hiday |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-0595cece42914d5e8f3e7147b23346a2 |
| institution | Kabale University |
| issn | 2090-5904 1687-5443 |
| language | English |
| publishDate | 2017-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Neural Plasticity |
| spelling | doaj-art-0595cece42914d5e8f3e7147b23346a22025-02-03T01:03:43ZengWileyNeural Plasticity2090-59041687-54432017-01-01201710.1155/2017/41530764153076Mechanisms and Consequences of Dopamine Depletion-Induced Attenuation of the Spinophilin/Neurofilament Medium InteractionAndrew C. Hiday0Michael C. Edler1Asma B. Salek2Cameron W. Morris3Morrent Thang4Tyler J. Rentz5Kristie L. Rose6Lisa M. Jones7Anthony J. Baucum8Department of Biology, Indiana University-Purdue University Indianapolis, 723 W. Michigan St., Indianapolis, IN 46202, USADepartment of Biology, Indiana University-Purdue University Indianapolis, 723 W. Michigan St., Indianapolis, IN 46202, USADepartment of Biology, Indiana University-Purdue University Indianapolis, 723 W. Michigan St., Indianapolis, IN 46202, USADepartment of Chemistry and Chemical Biology, Indiana University-Purdue University Indianapolis, 723 W. Michigan St., Indianapolis, IN 46202, USADepartment of Psychology, Indiana University-Purdue University Indianapolis, 723 W. Michigan St., Indianapolis, IN 46202, USAMolecular Physiology and Biophysics, Vanderbilt University School of Medicine University, 724 Robinson Research Building, 23rd Ave South at Pierce, Nashville, TN 37232, USADepartment 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, USADepartment of Chemistry and Chemical Biology, Indiana University-Purdue University Indianapolis, 723 W. Michigan St., Indianapolis, IN 46202, USADepartment of Biology, Indiana University-Purdue University Indianapolis, 723 W. Michigan St., Indianapolis, IN 46202, USASignaling 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.http://dx.doi.org/10.1155/2017/4153076 |
| spellingShingle | Andrew C. Hiday Michael C. Edler Asma B. Salek Cameron W. Morris Morrent Thang Tyler J. Rentz Kristie L. Rose Lisa M. Jones Anthony J. Baucum Mechanisms and Consequences of Dopamine Depletion-Induced Attenuation of the Spinophilin/Neurofilament Medium Interaction Neural Plasticity |
| title | Mechanisms and Consequences of Dopamine Depletion-Induced Attenuation of the Spinophilin/Neurofilament Medium Interaction |
| title_full | Mechanisms and Consequences of Dopamine Depletion-Induced Attenuation of the Spinophilin/Neurofilament Medium Interaction |
| title_fullStr | Mechanisms and Consequences of Dopamine Depletion-Induced Attenuation of the Spinophilin/Neurofilament Medium Interaction |
| title_full_unstemmed | Mechanisms and Consequences of Dopamine Depletion-Induced Attenuation of the Spinophilin/Neurofilament Medium Interaction |
| title_short | Mechanisms and Consequences of Dopamine Depletion-Induced Attenuation of the Spinophilin/Neurofilament Medium Interaction |
| title_sort | mechanisms and consequences of dopamine depletion induced attenuation of the spinophilin neurofilament medium interaction |
| url | http://dx.doi.org/10.1155/2017/4153076 |
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