Differential roles of NF-Y transcription factor in ER chaperone expression and neuronal maintenance in the CNS
Autor: | Asako Tosaki, Sankar N. Maity, Ryosuke Takahashi, Tomomi Shimogori, Yasuo Uchiyama, Tomoyuki Yamanaka, Nobuyuki Nukina, Masaru Kurosawa, Nobutaka Hattori, Hidemi Misawa, Masato Koike, Haruko Miyazaki |
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Jazyk: | angličtina |
Rok vydání: | 2016 |
Předmět: |
0301 basic medicine
Gene knockdown Genetics of the nervous system Multidisciplinary biology Endoplasmic reticulum Neurodegeneration medicine.disease Article Cell biology 03 medical and health sciences 030104 developmental biology Ubiquitin Downregulation and upregulation nervous system Chaperone (protein) Gene expression biology.protein medicine Transcription factor |
Zdroj: | Scientific Reports |
ISSN: | 2045-2322 |
DOI: | 10.1038/srep34575 |
Popis: | The mammalian central nervous system (CNS) contains various types of neurons with different neuronal functions. In contrast to established roles of cell type-specific transcription factors on neuronal specification and maintenance, whether ubiquitous transcription factors have conserved or differential neuronal function remains uncertain. Here, we revealed that inactivation of a ubiquitous factor NF-Y in different sets of neurons resulted in cell type-specific neuropathologies and gene downregulation in mouse CNS. In striatal and cerebellar neurons, NF-Y inactivation led to ubiquitin/p62 pathologies with downregulation of an endoplasmic reticulum (ER) chaperone Grp94, as we previously observed by NF-Y deletion in cortical neurons. In contrast, NF-Y inactivation in motor neurons induced neuronal loss without obvious protein deposition. Detailed analysis clarified downregulation of another ER chaperone Grp78 in addition to Grp94 in motor neurons and knockdown of both ER chaperones in motor neurons recapitulated the pathology observed after NF-Y inactivation. Finally, additional downregulation of Grp78 in striatal neurons suppressed ubiquitin accumulation induced by NF-Y inactivation, implying that selective ER chaperone downregulation mediates different neuropathologies. Our data suggest distinct roles of NF-Y in protein homeostasis and neuronal maintenance in the CNS by differential regulation of ER chaperone expression. |
Databáze: | OpenAIRE |
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