Altered subcellular localization of fragile X mental retardation signaling partners and targets in superior frontal cortex of individuals with schizophrenia
| Autor: | Timothy D. Folsom, Paul Thuras, S. Hossein Fatemi |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male congenital hereditary and neonatal diseases and abnormalities medicine.medical_specialty Protein subunit Population Prefrontal Cortex P70-S6 Kinase 1 Tissue Banks Biology 03 medical and health sciences Amyloid beta-Protein Precursor Fragile X Mental Retardation Protein 0302 clinical medicine Neurodevelopmental disorder Internal medicine mental disorders medicine Humans Phosphorylation education Aged Aged 80 and over education.field_of_study General Neuroscience Endoplasmic reticulum Ribosomal Protein S6 Kinases 70-kDa Protein phosphatase 2 Middle Aged medicine.disease Subcellular localization nervous system diseases Protein Phosphatase 2C 030104 developmental biology Endocrinology Schizophrenia Female Endoplasmic Reticulum Rough Neuroscience 030217 neurology & neurosurgery |
| Zdroj: | Neuroreport. 28(16) |
| ISSN: | 1473-558X |
| Popis: | Schizophrenia is a severe, debilitating, neurodevelopmental disorder that affects 1% of the world's population. Recent findings from our laboratory have identified reduced levels of fragile X mental retardation protein (FMRP) and several downstream FMRP targets in superior frontal cortex of individuals with schizophrenia. We hypothesized that altered subcellular expression of FMRP and its signaling partners may explain these changes. In the current study we employed subcellular fractionation and western blotting to determine levels of FMRP, phosphorylated-FMRP as well as selected signaling partners [protein phosphatase 2A catalytic subunit (PP2AC), p70 S6 kinase (p70 S6K), and amyloid-β A4 precursor protein (APP)] in the total homogenate, nuclear, and rough endoplasmic reticulum fractions in superior frontal cortex of individuals with schizophrenia versus controls (N=12/group). In total homogenate of individuals with schizophrenia, we identified significantly lower levels of FMRP, phosphorylated-FMRP, and PP2AC. In the nuclear fraction of individuals with schizophrenia we found significantly higher levels of PP2AC, p70 S6K, APP 120 kDa, and APP 88 kDa proteins. Finally, in rough endoplasmic reticulum of individuals with schizophrenia, we identified significantly lower protein levels of p70 S6K and APP 120 kDa. These results provide evidence for a potential mechanism to explain altered FMRP expression in schizophrenia. |
| Databáze: | OpenAIRE |
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