A novel non-canonical Notch signaling regulates expression of synaptic vesicle proteins in excitatory neurons

Yukari Hayashi, Hiroshi Nishimune, Katsuto Hozumi, Yumiko Saga, Akihiro Harada, Michisuke Yuzaki, Takeshi Iwatsubo, Raphael Kopan, Taisuke Tomita

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Notch signaling plays crucial roles for cellular differentiation during development through γ-secretase-dependent intramembrane proteolysis followed by transcription of target genes. Although recent studies implicate that Notch regulates synaptic plasticity or cognitive performance, the molecular mechanism how Notch works in mature neurons remains uncertain. Here we demonstrate that a novel Notch signaling is involved in expression of synaptic proteins in postmitotic neurons. Levels of several synaptic vesicle proteins including synaptophysin 1 and VGLUT1 were increased when neurons were cocultured with Notch ligands-expressing NIH3T3 cells. Neuron-specific deletion of Notch genes decreased these proteins, suggesting that Notch signaling maintains the expression of synaptic vesicle proteins in a cell-autonomous manner. Unexpectedly, cGMP-dependent protein kinase (PKG) inhibitor, but not γ-secretase inhibitor, abolished the elevation of synaptic vesicle proteins, suggesting that generation of Notch intracellular domain is dispensable for this function. These data uncover a ligand-dependent, but γ-secretase-independent, non-canonical Notch signaling involved in presynaptic protein expression in postmitotic neurons.

Original languageEnglish
Article number23969
JournalScientific reports
Volume6
DOIs
Publication statusPublished - 2016 Apr 4

ASJC Scopus subject areas

  • General

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    Hayashi, Y., Nishimune, H., Hozumi, K., Saga, Y., Harada, A., Yuzaki, M., Iwatsubo, T., Kopan, R., & Tomita, T. (2016). A novel non-canonical Notch signaling regulates expression of synaptic vesicle proteins in excitatory neurons. Scientific reports, 6, [23969]. https://doi.org/10.1038/srep23969