Differential roles of NF-Y transcription factor in ER chaperone expression and neuronal maintenance in the CNS

Tomoyuki Yamanaka, Asako Tosaki, Haruko Miyazaki, Masaru Kurosawa, Masato Koike, Yasuo Uchiyama, Sankar N. Maity, Hidemi Misawa, Ryosuke Takahashi, Tomomi Shimogori, Nobutaka Hattori, Nobuyuki Nukina

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6 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number34575
JournalScientific reports
Volume6
DOIs
Publication statusPublished - 2016 Sep 30

ASJC Scopus subject areas

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    Yamanaka, T., Tosaki, A., Miyazaki, H., Kurosawa, M., Koike, M., Uchiyama, Y., Maity, S. N., Misawa, H., Takahashi, R., Shimogori, T., Hattori, N., & Nukina, N. (2016). Differential roles of NF-Y transcription factor in ER chaperone expression and neuronal maintenance in the CNS. Scientific reports, 6, [34575]. https://doi.org/10.1038/srep34575