Rap1-PDZ-GEF1 interacts with a neurotrophin receptor at late endosomes, leading to sustained activation of Rap1 and ERK and neurite outgrowth.
Rap1-PDZ-GEF1 interacts with a neurotrophin receptor at late endosomes, leading to sustained activation of Rap1 and ERK and neurite outgrowth.
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DOI：
10.1083/jcb.200610073
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发表时间：
2007-08-27
期刊：
影响因子：
--
通讯作者：
Takai Y
中科院分区：
文献类型：
--
作者：
Hisata S;Sakisaka T;Baba T;Yamada T;Aoki K;Matsuda M;Takai Y
神经营养因子，如NGF和BDNF，诱导Rap 1小G蛋白和ERK的持续激活，这是神经突生长所必需的。我们表明参与的GDP/GTP交换因子（GEF）Rap 1，PDZ-GEF 1，在这些过程中。PDZ-GEF 1通过正反馈机制被GTP-Rap 1激活。在NGF结合后，TrkA神经营养因子受体从细胞表面内化，穿过早期内体，并到达晚期内体。PDZ-GEF 1、突触支架分子和富含锚蛋白重复序列的跨膜蛋白之间形成四聚体复合物，其直接与TrkA受体相互作用。在晚期内体，复合物诱导Rap 1和ERK的持续激活，导致神经突生长。在培养的大鼠海马神经元中，PDZ-GEF 1以BDNF依赖的方式被募集到晚期内体，参与BDNF诱导的神经突生长。因此，PDZ-GEF 1与转运到晚期内体的内化神经营养因子受体的相互作用诱导Rap 1和ERK的持续激活和神经突生长。
Neurotrophins, such as NGF and BDNF, induce sustained activation of Rap1 small G protein and ERK, which are essential for neurite outgrowth. We show involvement of a GDP/GTP exchange factor (GEF) for Rap1, PDZ-GEF1, in these processes. PDZ-GEF1 is activated by GTP-Rap1 via a positive feedback mechanism. Upon NGF binding, the TrkA neurotrophin receptor is internalized from the cell surface, passes through early endosomes, and arrives in late endosomes. A tetrameric complex forms between PDZ-GEF1, synaptic scaffolding molecule and ankyrin repeat-rich membrane spanning protein which interacts directly with the TrkA receptor. At late endosomes, the complex induces sustained activation of Rap1 and ERK, resulting in neurite outgrowth. In cultured rat hippocampal neurons, PDZ-GEF1 is recruited to late endosomes in a BDNF-dependent manner involved in BDNF-induced neurite outgrowth. Thus, the interaction of PDZ-GEF1 with an internalized neurotrophin receptor transported to late endosomes induces sustained activation of both Rap1 and ERK and neurite outgrowth.
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DOI：
10.1002/neu.10323
发表时间：
2004-02-05
期刊：
JOURNAL OF NEUROBIOLOGY
影响因子：
--
作者：
Howe, CL;Mobley, WC
通讯作者：
Mobley, WC
影响因子：
30.5
作者：
Katagiri, Koko;Imamura, Masashi;Kinashi, Tatsuo
通讯作者：
Kinashi, Tatsuo
影响因子：
16.2
作者：
Howe, CL;Valletta, JS;Mobley, WC
通讯作者：
Mobley, WC
影响因子：
4.8
作者：
Hirao, K;Hata, Y;Takai, Y
通讯作者：
Takai, Y
影响因子：
4.8
作者：
Arévolo, JC;Pereira, DB;Chao, MV
通讯作者：
Chao, MV