The murine ortholog of Kaufman oculocerebrofacial syndrome gene Ube3b is crucial for the maintenance of the excitatory synapses in the young adult stage

Saki Katsube; Noriko Koganezawa; Kenji Hanamura; Katherine J Cuthill; Victor Tarabykin; Mateusz C Ambrozkiewicz; Hiroshi Kawabe

doi:10.1016/j.neulet.2023.137059

The murine ortholog of Kaufman oculocerebrofacial syndrome gene Ube3b is crucial for the maintenance of the excitatory synapses in the young adult stage

Neurosci Lett. 2023 Feb 16:797:137059. doi: 10.1016/j.neulet.2023.137059. Epub 2023 Jan 7.

Authors

Saki Katsube¹, Noriko Koganezawa², Kenji Hanamura³, Katherine J Cuthill⁴, Victor Tarabykin⁵, Mateusz C Ambrozkiewicz⁴, Hiroshi Kawabe⁶

Affiliations

¹ Department of Pharmacology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan; Gunma University School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan.
² Department of Pharmacology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan. Electronic address: n-koganezawa@gunma-u.ac.jp.
³ Department of Pharmacology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan.
⁴ Institute of Cell Biology and Neurobiology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany.
⁵ Institute of Cell Biology and Neurobiology, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Charitéplatz 1, 10117 Berlin, Germany; Institute of Neuroscience, Lobachevsky State University of Nizhny Novgorod, Nizhny Novgorod 603950, Russia; Research Institute of Medical Genetics, Tomsk National Research Medical Center of the Russian Academy of Sciences, Tomsk 634009, Russia.
⁶ Department of Pharmacology, Gunma University Graduate School of Medicine, 3-39-22 Showa-machi, Maebashi, Gunma 371-8511, Japan. Electronic address: kawabe@gunma-u.ac.jp.

PMID: 36623761
DOI: 10.1016/j.neulet.2023.137059

Abstract

Kaufman oculocerebrofacial syndrome (KOS) is an autosomal recessive developmental disorder. Inactivating mutations in UBE3B, an E3 ubiquitin ligase gene are causative for KOS. We have reported that towards postnatal week three, its murine ortholog, Ube3b, acts as a negative regulator of the number of dendritic spines. In this study, we investigated the role of Ube3b at the synapse in the young adult mice. With an improved estimation method, images from the hippocampal CA1 and CA2 regions acquired with 3D Stimulated Emission Depletion (3D-STED) microscopy were used to quantify the excitatory synapse numbers. In the young adult mice, the excitatory synapse density was decreased in brain-specific Ube3b conditional knockout mice as compared to the control. Our results indicate the novel role of Ube3b in the maintenance of synapse numbers in the young adult period.

Keywords: Hippocampal CA1 region; Hippocampal CA2 region; Kaufman oculocerebrofacial syndrome (KOS); Super-resolved stimulated emission depletion (STED) microscopy; Synapse; Ube3b.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Eye Abnormalities / genetics
Intellectual Disability / genetics
Mice
Microcephaly / genetics
Synapses* / metabolism
Ubiquitin-Protein Ligases* / genetics
Ubiquitin-Protein Ligases* / metabolism

Substances

Ubiquitin-Protein Ligases
Ube3b protein, mouse

Supplementary concepts

Kaufman oculocerebrofacial syndrome