The ataxia (axJ) mutation causes abnormal GABAA receptor turnover in mice.
Standard
The ataxia (axJ) mutation causes abnormal GABAA receptor turnover in mice. / Lappe-Siefke, Corinna; Löbrich, Sven; Hevers, Wulf; Waidmann, Oliver B; Schweizer, Michaela; Fehr, Susanne; Fritschy, Jean-Marc; Dikic, Ivan; Eilers, Jens; Wilson, Scott M; Kneussel, Matthias.
in: PLOS GENET, Jahrgang 5, Nr. 9, 9, 2009, S. 1000631.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - The ataxia (axJ) mutation causes abnormal GABAA receptor turnover in mice.
AU - Lappe-Siefke, Corinna
AU - Löbrich, Sven
AU - Hevers, Wulf
AU - Waidmann, Oliver B
AU - Schweizer, Michaela
AU - Fehr, Susanne
AU - Fritschy, Jean-Marc
AU - Dikic, Ivan
AU - Eilers, Jens
AU - Wilson, Scott M
AU - Kneussel, Matthias
PY - 2009
Y1 - 2009
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 ax(J) gene locus, encoding the ubiquitin-specific protease 14 (Usp14), negatively influences synaptic receptor turnover. Ax(J) mouse mutants, characterized by cerebellar ataxia, display both increased GABA(A) receptor (GABA(A)R) levels at PC surface membranes accompanied by enlarged IPSCs. Accordingly, we identify physical interaction of Usp14 and the GABA(A)R alpha1 subunit. Although other currently unknown changes might be involved, our data show that ubiquitin-dependent GABA(A)R turnover at cerebellar synapses contributes to ax(J)-mediated behavioural impairment.
AB - 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 ax(J) gene locus, encoding the ubiquitin-specific protease 14 (Usp14), negatively influences synaptic receptor turnover. Ax(J) mouse mutants, characterized by cerebellar ataxia, display both increased GABA(A) receptor (GABA(A)R) levels at PC surface membranes accompanied by enlarged IPSCs. Accordingly, we identify physical interaction of Usp14 and the GABA(A)R alpha1 subunit. Although other currently unknown changes might be involved, our data show that ubiquitin-dependent GABA(A)R turnover at cerebellar synapses contributes to ax(J)-mediated behavioural impairment.
U2 - 10.1371/journal.pgen.1000631
DO - 10.1371/journal.pgen.1000631
M3 - SCORING: Zeitschriftenaufsatz
VL - 5
SP - 1000631
JO - PLOS GENET
JF - PLOS GENET
SN - 1553-7404
IS - 9
M1 - 9
ER -