• UBE3A controls axon initial se...

*Result*: UBE3A controls axon initial segment in the cortical pyramidal neurons.

Title:
UBE3A controls axon initial segment in the cortical pyramidal neurons.
Authors:
Liu X; Department of Anatomy and Neuroscience, Faculty of Medicine, Shimane University, Izumo, 693-8501, Japan., Jiang Z; Department of Anatomy and Neuroscience, Faculty of Medicine, Shimane University, Izumo, 693-8501, Japan; Ningxia Key Laboratory of Craniocerebral Diseases, Ningxia Medical University, 1160 Shengli Street, Yinchuan, 750004, Ningxia, China., Otani Y; Department of Anatomy and Neuroscience, Faculty of Medicine, Shimane University, Izumo, 693-8501, Japan., Zhu X; Department of Anatomy and Neuroscience, Faculty of Medicine, Shimane University, Izumo, 693-8501, Japan., Yu Y; Department of Anatomy and Neuroscience, Faculty of Medicine, Shimane University, Izumo, 693-8501, Japan., Tarif AMM; Department of Anatomy and Neuroscience, Faculty of Medicine, Shimane University, Izumo, 693-8501, Japan., Ferdousy RN; Department of Anatomy and Neuroscience, Faculty of Medicine, Shimane University, Izumo, 693-8501, Japan., Kishino T; Division of Functional Genomics, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan., Fujitani M; Department of Anatomy and Neuroscience, Faculty of Medicine, Shimane University, Izumo, 693-8501, Japan. Electronic address: fujitani@med.shimane-u.ac.jp.
Source:
Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2025 Mar 05; Vol. 751, pp. 151429. Date of Electronic Publication: 2025 Feb 01.
Publication Type:
Journal Article; Research Support, Non-U.S. Gov't
Language:
English
Journal Info:
Publisher: Elsevier Country of Publication: United States NLM ID: 0372516 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1090-2104 (Electronic) Linking ISSN: 0006291X NLM ISO Abbreviation: Biochem Biophys Res Commun Subsets: MEDLINE
Imprint Name(s):
Publication: <2002- >: San Diego, CA : Elsevier
Original Publication: New York, Academic Press.
MeSH Terms:
Pyramidal Cells*/metabolism , Pyramidal Cells*/cytology , Pyramidal Cells*/physiology , Ubiquitin-Protein Ligases*/metabolism , Ubiquitin-Protein Ligases*/genetics , Ubiquitin-Protein Ligases*/physiology , Axon Initial Segment*/metabolism , Axon Initial Segment*/physiology , Cerebral Cortex*/cytology , Axons*/metabolism, Prefrontal Cortex/cytology ; Animals ; Mice ; Cells, Cultured ; Mice, Inbred C57BL ; Mice, Knockout
Contributed Indexing:
Keywords: Angelman syndrome; Axon initial segment; Prelimbic cortex; Pyramidal neurons; Ubiquitin-protein ligase E3A
Substance Nomenclature:
EC 2.3.2.27 (Ubiquitin-Protein Ligases)
EC 2.3.2.26 (Ube3a protein, mouse)
Entry Date(s):
Date Created: 20250206 Date Completed: 20250506 Latest Revision: 20250526
Update Code:
20260130
DOI:
10.1016/j.bbrc.2025.151429
PMID:
39914145
Database:
MEDLINE

*Further Information*

*The axon initial segment (AIS) is a critical regulator of neuronal excitability and the initiation site of action potentials. Alterations in the structural features of AIS, such as length and position, have been shown to influence neuronal function, a phenomenon known as activity-dependent AIS plasticity. In addition to their physiological functions, abnormalities in the AIS have been implicated in various neurological disorders. UBE3A is an E3 ubiquitin ligase crucial for protein degradation in neurons. In mature neurons, only the maternal allele of the UBE3A gene is active, and the paternal allele is silenced. However, the role of UBE3A in controlling AIS in the cortical pyramidal neurons has not yet been fully elucidated. In this study, we compared wild-type mice with three different Ube3a-deficient mice and observed specific elongation of the AIS in the prelimbic cortex of the medial prefrontal cortex but not in the somatosensory cortex or motor cortex, as previously reported. Interestingly, we also showed that UBE3A controls AIS length in a cell-autonomous manner using cultured cortical neurons derived from Ube3a-floxed (Ube3a<sup>flox/flox</sup>) mice. This study indicates that UBE3A controls AIS length through a cell-autonomous mechanism in vitro. However, non-cell-autonomous mechanisms, including feedback from inhibitory neurons or connections with the hippocampus, may also influence adult AIS length in vivo, thereby helping to maintain the excitability homeostasis of cortical pyramidal neurons in a region-specific manner.
(Copyright © 2025 Elsevier Inc. All rights reserved.)*

*Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.*