TY  - JOUR
A1  - Lappe-Siefke, Corinna
A1  - Löbrich, Sven
A1  - Hevers, Wulf
A1  - Waidmann, Oliver
A1  - Schweizer, Michaela
A1  - Fehr, Susanne
A1  - Fritschy, Jean-Marc
A1  - Đikić, Ivan
A1  - Eilers, Jens
A1  - Wilson, Scott M.
A1  - Kneussel, Matthias
T1  - The ataxia (axJ) mutation causes abnormal GABAA receptor turnover in mice
T2  - PLoS genetics
N2  - 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.
Y1  - 2009
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/22564
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30-114197
SN  - 1553-7404
N1  - 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.
VL  - 5
IS  - (9): e1000631
ER  -