Fbxo45, a novel ubiquitin ligase, regulates synaptic activity

Hirobumi Tada, Hirotaka James Okano, Hiroshi Takagi, Shinsuke Shibata, Ikuko Yao, Masaki Matsumoto, Toru Saiga, Keiichi I. Nakayama, Haruo Kashima, Takuya Takahashi, Mitsutoshi Setou, Hideyuki Okano

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

Neurons communicate with each other through synapses. To establish the precise yet flexible connections that make up neural networks in the brain, continuous synaptic modulation is required. The ubiquitin-proteasome system of protein degradation is one of the critical mechanisms that underlie this process, playing crucial roles in the regulation of synaptic structure and function. We identified a novel ubiquitin ligase, Fbxo45, that functions at synapses. Fbxo45 is evolutionarily conserved and selectively expressed in the nervous system. We demonstrated that the knockdown of Fbxo45 in primary cultured hippocampal neurons resulted in a greater frequency of miniature excitatory postsynaptic currents. We also found that Fbxo45 induces the degradation of a synaptic vesicle-priming factor, Munc13-1.We propose that Fbxo45 plays an important role in the regulation of neurotransmission by modulating Munc13-1 at the synapse.

Original languageEnglish
Pages (from-to)3840-3849
Number of pages10
JournalJournal of Biological Chemistry
Volume285
Issue number6
DOIs
Publication statusPublished - 2010 Feb 5

Fingerprint

Ligases
Ubiquitin
Synapses
Neurons
Degradation
Neurology
Proteasome Endopeptidase Complex
Brain
Synaptic Vesicles
Excitatory Postsynaptic Potentials
Modulation
Neural networks
Synaptic Transmission
Nervous System
Proteolysis
Proteins

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology
  • Medicine(all)

Cite this

Fbxo45, a novel ubiquitin ligase, regulates synaptic activity. / Tada, Hirobumi; Okano, Hirotaka James; Takagi, Hiroshi; Shibata, Shinsuke; Yao, Ikuko; Matsumoto, Masaki; Saiga, Toru; Nakayama, Keiichi I.; Kashima, Haruo; Takahashi, Takuya; Setou, Mitsutoshi; Okano, Hideyuki.

In: Journal of Biological Chemistry, Vol. 285, No. 6, 05.02.2010, p. 3840-3849.

Research output: Contribution to journalArticle

Tada, H, Okano, HJ, Takagi, H, Shibata, S, Yao, I, Matsumoto, M, Saiga, T, Nakayama, KI, Kashima, H, Takahashi, T, Setou, M & Okano, H 2010, 'Fbxo45, a novel ubiquitin ligase, regulates synaptic activity', Journal of Biological Chemistry, vol. 285, no. 6, pp. 3840-3849. https://doi.org/10.1074/jbc.M109.046284
Tada, Hirobumi ; Okano, Hirotaka James ; Takagi, Hiroshi ; Shibata, Shinsuke ; Yao, Ikuko ; Matsumoto, Masaki ; Saiga, Toru ; Nakayama, Keiichi I. ; Kashima, Haruo ; Takahashi, Takuya ; Setou, Mitsutoshi ; Okano, Hideyuki. / Fbxo45, a novel ubiquitin ligase, regulates synaptic activity. In: Journal of Biological Chemistry. 2010 ; Vol. 285, No. 6. pp. 3840-3849.
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