The ataxia (axJ) mutation causes abnormal GABAA receptor turnover in mice

  • Ataxia represents a pathological coordination failure that often involves functional disturbances in cerebellar circuits. Purkinje cells (PCs) characterize the only output neurons of the cerebellar cortex and critically participate in regulating motor coordination. Although different genetic mutations are known that cause ataxia, little is known about the underlying cellular mechanisms. Here we show that a mutated axJ gene locus, encoding the ubiquitin-specific protease 14 (Usp14), negatively influences synaptic receptor turnover. AxJ mouse mutants, characterized by cerebellar ataxia, display both increased GABAA receptor (GABAAR) levels at PC surface membranes accompanied by enlarged IPSCs. Accordingly, we identify physical interaction of Usp14 and the GABAAR alpha 1 subunit. Although other currently unknown changes might be involved, our data show that ubiquitin-dependent GABAAR turnover at cerebellar synapses contributes to axJ-mediated behavioural impairment.

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Metadaten
Author:Corinna Lappe-Siefke, Sven Löbrich, Wulf Hevers, Oliver WaidmannORCiDGND, Michaela Schweizer, Susanne Fehr, Jean-Marc Fritschy, Ivan ĐikićORCiDGND, Jens Eilers, Scott M. Wilson, Matthias Kneussel
URN:urn:nbn:de:hebis:30-114197
DOI:https://doi.org/10.1371/journal.pgen.1000631
ISSN:1553-7404
Parent Title (English):PLoS genetics
Document Type:Article
Language:English
Year of Completion:2009
Year of first Publication:2009
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2011/09/01
Volume:5
Issue:(9): e1000631
Note:
Copyright: © 2009 Lappe-Siefke et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Source:PLoS Genetics 5(9): e1000631. doi: 10.1371/journal.pgen.1000631
HeBIS-PPN:274985411
Institutes:Biochemie, Chemie und Pharmazie / Biochemie und Chemie
Medizin / Medizin
Dewey Decimal Classification:5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie
Sammlungen:Universitätspublikationen
Sammlung Biologie / Sondersammelgebiets-Volltexte
Licence (German):License LogoCreative Commons - Namensnennung 3.0