Neuronal F-Box protein FBXO41 regulates synaptic transmission and hippocampal network maturation

Ana R.A.A. Quadros, Rocío Díez Arazola, Andrea Romaguera Álvarez, Johny Pires, Rhiannon M. Meredith, Ingrid Saarloos, Matthijs Verhage, Ruud F. Toonen

Research output: Contribution to journalArticleAcademicpeer-review

2 Citations (Scopus)

Abstract

FBXO41 is a neuron-specific E3 ligase subunit implicated in epileptic encephalopathies. Fbxo41 null mutant (KO) mice show behavioral deficits and early lethality. Here, we report that loss of FBXO41 causes defects in synaptic transmission and brain development. Cultured Fbxo41 KO neurons had normal morphology and showed no signs of degeneration. Single-cell electrophysiology showed a lower synaptic vesicle release probability in excitatory neurons. Inhibitory neurons exhibited reduced synaptophysin expression, a smaller readily releasable pool, and decreased charge transfer during repetitive stimulation. In Fbxo41 KO hippocampal slices at postnatal day 6, the dentate gyrus was smaller with fewer radial-glial-like cells and immature neurons. In addition, neuronal migration was delayed. Two-photon calcium imaging showed a delayed increase in network activity and synchronicity. Together, our findings point toward a role for FBXO41 in synaptic transmission and postnatal brain development, before behavioral deficits are detected in Fbxo41 KO mice.

Original languageEnglish
Article number104069
Pages (from-to)1-18
Number of pages19
JournaliScience
Volume25
Issue number4
Early online date18 Mar 2022
DOIs
Publication statusPublished - 15 Apr 2022

Keywords

  • Cellular neuroscience
  • Developmental neuroscience
  • Molecular neuroscience

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