A function of huntingtin in guanine nucleotide exchange on RabII

被引:49
作者
Li, Xueyi [1 ,2 ]
Sapp, Ellen [2 ]
Valencia, Antonio [2 ]
Kegel, Kimberly B. [2 ]
Qin, Zheng-Hong [2 ]
Alexander, Jonathan [2 ]
Masso, Nicholas [2 ]
Reeves, Patrick [2 ]
Ritch, James J. [2 ]
Zeitlin, Scott [4 ]
Aronin, Neil [3 ]
DiFiglia, Marian [2 ]
机构
[1] Harvard Univ, Sch Med, Massachusetts Gen Hosp, Lab Cellular Neurobiol, Charlestown, MA 02129 USA
[2] Massachusetts Gen Hosp, Dept Neurol, Charlestown, MA USA
[3] Univ Massachusetts, Sch Med, Dept Med & Cell Biol, Worcester, MA USA
[4] Univ Virginia, Sch Med, Dept Neurosci, Charlottesville, VA 22908 USA
关键词
endosomes; huntingtin; nucleotide exchange factor; RabII;
D O I
10.1097/WNR.0b013e328315cd4c
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Huntingtin is ubiquitously expressed and enriched in the brain. Deletion of the huntingtin gene in mice is lethal during early embryonic development. The function of huntingtin is, however, not clear. Here, we report that huntingtin is important for the function of RabII, a critical GTPase in regulating membrane traffic from recycling endosomes to the plasma membrane. In huntingtinnull embryonic cells, the levels of RabII on membranes nucleotide exchange activity on RabII were significantly reduced compared with normal embryonic stem cells. In brain membranes, an antibody against huntingtin immunoprecipitated a nucleoticle exchange activity on RabII and huntingtin was coprecipitated with RabII in the presence of guanosine diphosphate. These data suggest a role for huntingtin in a complex that activates RabII. NeuroReport 19:1643-1647 (C) 2008 Wolters Kluwer Health | Lippincott Williams & Wilkins.
引用
收藏
页码:1643 / 1647
页数:5
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