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Phosphorylation State Modulates the Interaction Between Neurofilament Medium and Spinophilin
Author(s) -
Hiday Andrew,
Edler Jr Michael,
Rentz Tyler,
Baucum Anthony
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.771.16
Subject(s) - microbiology and biotechnology , medium spiny neuron , scaffold protein , phosphorylation , neurofilament , protein subunit , dendritic spine , chemistry , axoplasmic transport , neuroscience , kinase , biology , signal transduction , biochemistry , striatum , immunohistochemistry , hippocampal formation , gene , dopamine , immunology
In Parkinson's Disease (PD) there is both a structural and functional loss of dendritic spines on striatal medium spiny neurons (MSNs). However, the full mechanisms underlying functional and structural changes in striatal MSNs are not completely clear. Spine morphology and striatal MSN physiology are regulated by an array of structural and scaffolding proteins. Two such proteins are spinophilin, a protein phosphatase 1 and F‐actin binding protein, and the intermediate filament protein, neurofilament medium (NFM). Here we show that these two proteins interact in brain tissue and when overexpressed in a heterologous cell system. Interestingly, in a preliminary proteomics screen, the interaction of spinophilin with NFM was reduced in 6‐hydroxydopamine‐lesioned mice, a model of PD. It is known that there is a misregulation of multiple protein kinases in many neurodegenerative diseases, including PD. Interestingly, we have found that overexpression of the catalytic subunit of protein kinase A (PKA) along with spinophilin and NFM in a heterologous cell system increases the interaction between spinophilin and NF‐M. The implications of this altered association and modulation of spinophilin and NFM phosphorylation in PD will be discussed.