Rabex-5 determines the neurite localization of its downstream Rab proteins in hippocampal neurons.
Rabex-5 determines the neurite localization of its downstream Rab proteins in hippocampal neurons.
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DOI：
10.4161/cib.25433
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发表时间：
2013-09-01
影响因子：
--
通讯作者：
Fukuda M
中科院分区：
文献类型：
--
作者：
Mori Y;Fukuda M
Rab家族小gtpase在调节细胞膜交通中起分子开关作用，其活性被认为是由鸟嘌呤核苷酸交换因子（gef）控制的。然而，gef在将Rab蛋白靶向到特定膜室中的作用尚不清楚。我们最近报道发现Rabex-5，最初被描述为Rab5-GEF，在小鼠海马神经元中也具有Rab17-GEF的功能。发育中的海马神经元中的Rab17特异性靶向树突而非轴突，Rabex-5的GEF活性是Rab17从细胞体转运到树突的必要条件。有趣的是，Rabex-5也是海马神经元中Rab5和Rab21的轴突和树突定位所必需的。我们的研究结果表明，Rabex-5决定其下游rabb蛋白靶向树突（Rab17）或轴突和树突（Rab5和Rab21）。
Rab family small GTPases function as molecular switches in the regulation of membrane traffic, and their activity is thought to be controlled by guanine nucleotide exchange factors (GEFs). However, the role of GEFs in targeting Rab proteins to specific membrane compartments is poorly understood. We have recently reported finding that Rabex-5, originally described as a Rab5-GEF, also functions as a Rab17-GEF in mouse hippocampal neurons. The Rab17 in developing hippocampal neurons is specifically targeted to their dendrites and not to their axons, and the GEF activity of Rabex-5 is required for translocation of Rab17 from the cell body to the dendrites. Interestingly, Rabex-5 is also required for the axon and dendrite localization of Rab5 and Rab21 in hippocampal neurons. Our findings indicate that Rabex-5 determines the targeting of its downstream Rab proteins to the dendrites (Rab17) or to both the axon and dendrites (Rab5 and Rab21).