Mechanisms and Consequences of Dopamine Depletion-Induced Attenuation of the Spinophilin/Neurofilament Medium Interaction
Autor: | Michael C. Edler, Asma B. Salek, Anthony J. Baucum, Tyler J. Rentz, Cameron W. Morris, Andrew C. Hiday, Lisa M. Jones, Kristie L. Rose, Morrent Thang |
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Jazyk: | angličtina |
Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
Male Proteomics Dendritic spine Article Subject Dopamine Phosphatase Nerve Tissue Proteins Biology lcsh:RC321-571 03 medical and health sciences Neurofilament Proteins medicine Animals Humans Phosphorylation Protein kinase A lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry Kinase Microfilament Proteins Protein phosphatase 1 Cyclin-Dependent Kinase 5 Parkinson Disease Cyclic AMP-Dependent Protein Kinases Corpus Striatum Cell biology Mice Inbred C57BL 030104 developmental biology HEK293 Cells Neurology Biochemistry Neurology (clinical) Postsynaptic density medicine.drug Research Article |
Zdroj: | Neural Plasticity, Vol 2017 (2017) Neural Plasticity |
ISSN: | 1687-5443 2090-5904 |
Popis: | 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. |
Databáze: | OpenAIRE |
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