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Altered social behavior and neuronal development in mice lacking the Uba6-Use1 ubiquitin transfer system.
- Source :
-
Molecular cell [Mol Cell] 2013 Apr 25; Vol. 50 (2), pp. 172-84. Date of Electronic Publication: 2013 Mar 14. - Publication Year :
- 2013
-
Abstract
- The Uba6 (E1)-Use1 (E2) ubiquitin transfer cascade is a poorly understood alternative arm of the ubiquitin proteasome system (UPS) and is required for mouse embryonic development, independent of the canonical Uba1-E2-E3 pathway. Loss of neuronal Uba6 during embryonic development results in altered patterning of neurons in the hippocampus and the amygdala, decreased dendritic spine density, and numerous behavioral disorders. The levels of the E3 ubiquitin ligase Ube3a (E6-AP) and Shank3, both linked with dendritic spine function, are elevated in the amygdala of Uba6-deficient mice, while levels of the Ube3a substrate Arc are reduced. Uba6 and Use1 promote proteasomal turnover of Ube3a in mouse embryo fibroblasts (MEFs) and catalyze Ube3a ubiquitylation in vitro. These activities occur in parallel with an independent pathway involving Uba1-UbcH7, but in a spatially distinct manner in MEFs. These data reveal an unanticipated role for Uba6 in neuronal development, spine architecture, mouse behavior, and turnover of Ube3a.<br /> (Copyright © 2013 Elsevier Inc. All rights reserved.)
- Subjects :
- Amygdala enzymology
Amygdala pathology
Animals
Body Weight
CA3 Region, Hippocampal enzymology
CA3 Region, Hippocampal pathology
Cells, Cultured
Dendritic Spines pathology
Embryonic Development
Energy Metabolism
Female
Genes, Lethal
Learning Disabilities metabolism
Locomotion
Male
Memory Disorders metabolism
Mice
Mice, Inbred C57BL
Mice, Knockout
Microfilament Proteins
Nerve Tissue Proteins metabolism
Oxygen Consumption
Protein Stability
Protein Structure, Tertiary
Qc-SNARE Proteins genetics
Qc-SNARE Proteins physiology
SNARE Proteins
Social Behavior
Ubiquitin-Activating Enzymes genetics
Ubiquitin-Activating Enzymes physiology
Ubiquitin-Protein Ligases metabolism
Vesicular Transport Proteins
Amygdala abnormalities
CA3 Region, Hippocampal abnormalities
Qc-SNARE Proteins deficiency
Ubiquitin-Activating Enzymes deficiency
Ubiquitination
Subjects
Details
- Language :
- English
- ISSN :
- 1097-4164
- Volume :
- 50
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Molecular cell
- Publication Type :
- Academic Journal
- Accession number :
- 23499007
- Full Text :
- https://doi.org/10.1016/j.molcel.2013.02.014