Disruption of Rab11 activity in a knock-in mouse model of Huntington's disease.
Disruption of Rab11 activity in a knock-in mouse model of Huntington's disease.
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DOI：
10.1016/j.nbd.2009.08.003
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发表时间：
2009-11
影响因子：
6.1
通讯作者：
Difiglia M
中科院分区：
文献类型：
--
作者：
Li X;Sapp E;Chase K;Comer-Tierney LA;Masso N;Alexander J;Reeves P;Kegel KB;Valencia A;Esteves M;Aronin N;Difiglia M
The Huntington's disease (HD) mutation causes polyglutamine expansion in huntingtin (Htt) and neurodegeneration. Htt interacts with a complex containing Rab11GDP and is involved in activation of Rab11, which functions in endosomal recycling and neurite growth and long-term potentiation. Like other Rab proteins, Rab11GDP undergoes nucleotide exchange to Rab11GTP for its activation. Here we show that striatal membranes of HD140Q/140Q knock-in mice are impaired in supporting conversion of Rab11GDP to Rab11GTP. Dominant negative Rab11 expressed in the striatum and cortex of normal mice caused neuropathology and motor dysfunction, suggesting that a deficiency in Rab11 activity is pathogenic in vivo. Primary cortical neurons from HD140Q/140Q mice were delayed in recycling transferrin receptors back to the plasma membrane. Partial rescue from glutamate induced cell death occurred in HD neurons expressing dominant active Rab11. We propose a novel mechanism of HD pathogenesis arising from diminished Rab11 activity at recycling endosomes.
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影响因子：
3.3
作者：
Hickey MA;Kosmalska A;Enayati J;Cohen R;Zeitlin S;Levine MS;Chesselet MF
通讯作者：
Chesselet MF
影响因子：
11.2
作者：
DURE, LS;YOUNG, AB;PENNEY, JB
通讯作者：
PENNEY, JB
影响因子：
16.2
作者：
DIFIGLIA, M;SAPP, E;ARONIN, N
通讯作者：
ARONIN, N
影响因子：
3.3
作者：
Jones, S;Newman, C;Segev, N
通讯作者：
Segev, N
影响因子：
64.5
作者：
Emery, G;Hutterer, A;Knoblich, JA
通讯作者：
Knoblich, JA