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

Autor: Ana R.A.A. Quadros, Rocío Díez Arazola, Andrea Romaguera Álvarez, Johny Pires, Rhiannon M. Meredith, Ingrid Saarloos, Matthijs Verhage, Ruud F. Toonen
Přispěvatelé: Human genetics, Amsterdam Neuroscience - Cellular & Molecular Mechanisms, Amsterdam Neuroscience - Compulsivity, Impulsivity & Attention, Functional Genomics, Integrative Neurophysiology
Rok vydání: 2021
Předmět:
Zdroj: iScience, 25(4):104069. Elsevier Inc.
Quadros, A R A A, Arazola, R D, Álvarez, A R, Pires, J, Meredith, R M, Saarloos, I, Verhage, M & Toonen, R F 2022, ' Neuronal F-Box protein FBXO41 regulates synaptic transmission and hippocampal network maturation ', iScience, vol. 25, no. 4, 104069, pp. 1-18 . https://doi.org/10.1016/j.isci.2022.104069
Quadros, A R A A, Arazola, R D E, Álvarez, A R, Pires, J, Meredith, R M, Saarloos, I, Verhage, M & Toonen, R F 2022, ' Neuronal F-Box protein FBXO41 regulates synaptic transmission and hippocampal network maturation ', iScience, vol. 25, no. 4, 104069 . https://doi.org/10.1016/j.isci.2022.104069
iScience, 25(4):104069, 1-18. Elsevier
ISSN: 2589-0042
DOI: 10.1016/j.isci.2022.104069
Popis: 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.
Databáze: OpenAIRE
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