Back to Search
Start Over
NF-Y inactivation causes atypical neurodegeneration characterized by ubiquitin and p62 accumulation and endoplasmic reticulum disorganization
- Source :
- Nature communications. 5
- Publication Year :
- 2013
-
Abstract
- Nuclear transcription factor-Y (NF-Y), a key regulator of cell-cycle progression, often loses its activity during differentiation into nonproliferative cells. In contrast, NF-Y is still active in mature, differentiated neurons, although its neuronal significance remains obscure. Here we show that conditional deletion of the subunit NF-YA in postmitotic mouse neurons induces progressive neurodegeneration with distinctive ubiquitin/p62 pathology; these proteins are not incorporated into filamentous inclusion but co-accumulated with insoluble membrane proteins broadly on endoplasmic reticulum (ER). The degeneration also accompanies drastic ER disorganization, that is, an aberrant increase in ribosome-free ER in the perinuclear region, without inducing ER stress response. We further perform chromatin immunoprecipitation and identify several NF-Y physiological targets including Grp94 potentially involved in ER disorganization. We propose that NF-Y is involved in a unique regulation mechanism of ER organization in mature neurons and its disruption causes previously undescribed novel neuropathology accompanying abnormal ubiquitin/p62 accumulation.
- Subjects :
- Sequestosome-1 Protein
Male
Protein subunit
General Physics and Astronomy
Endoplasmic Reticulum
General Biochemistry, Genetics and Molecular Biology
Mice
Ubiquitin
Cell Line, Tumor
medicine
Animals
HSP70 Heat-Shock Proteins
Heat-Shock Proteins
Adaptor Proteins, Signal Transducing
Multidisciplinary
biology
Endoplasmic reticulum
Neurodegeneration
Signal transducing adaptor protein
Membrane Proteins
Neurodegenerative Diseases
General Chemistry
medicine.disease
Endoplasmic Reticulum Stress
Molecular biology
Cell biology
Mice, Inbred C57BL
Membrane protein
CCAAT-Binding Factor
biology.protein
Female
Chromatin immunoprecipitation
Subjects
Details
- ISSN :
- 20411723
- Volume :
- 5
- Database :
- OpenAIRE
- Journal :
- Nature communications
- Accession number :
- edsair.doi.dedup.....549661cebef5e0dca33705dd7486f771