Details

Autor(en) / Beteiligte

• Ambrozkiewicz, Mateusz C
• Borisova, Ekaterina
• Schwark, Manuela
• Ripamonti, Silvia
• Schaub, Theres
• Smorodchenko, Alina
• Weber, A Ioana
• Rhee, Hong Jun
• Altas, Bekir
• Yilmaz, Rüstem
• Mueller, Susanne
• Piepkorn, Lars
• Horan, Stephen T
• Straussberg, Rachel
• Zaqout, Sami
• Jahn, Olaf
• Dere, Ekrem
• Rosário, Marta
• Boehm-Sturm, Philipp
• Borck, Guntram
• Willig, Katrin I
• Rhee, JeongSeop
• Tarabykin, Victor
• Kawabe, Hiroshi

Titel

The murine ortholog of Kaufman oculocerebrofacial syndrome protein Ube3b regulates synapse number by ubiquitinating Ppp3cc

Ist Teil von

• Molecular psychiatry, 2021-06, Vol.26 (6), p.1980-1995

Ort / Verlag

England: Nature Publishing Group

Erscheinungsjahr

2021

Quelle

MEDLINE

Beschreibungen/Notizen

• Kaufman oculocerebrofacial syndrome (KOS) is a severe autosomal recessive disorder characterized by intellectual disability, developmental delays, microcephaly, and characteristic dysmorphisms. Biallelic mutations of UBE3B, encoding for a ubiquitin ligase E3B are causative for KOS. In this report, we characterize neuronal functions of its murine ortholog Ube3b and show that Ube3b regulates dendritic branching in a cell-autonomous manner. Moreover, Ube3b knockout (KO) neurons exhibit increased density and aberrant morphology of dendritic spines, altered synaptic physiology, and changes in hippocampal circuit activity. Dorsal forebrain-specific Ube3b KO animals show impaired spatial learning, altered social interactions, and repetitive behaviors. We further demonstrate that Ube3b ubiquitinates the catalytic γ-subunit of calcineurin, Ppp3cc, the overexpression of which phenocopies Ube3b loss with regard to dendritic spine density. This work provides insights into the molecular pathologies underlying intellectual disability-like phenotypes in a genetically engineered mouse model.