NGF signaling from clathrin-coated vesicles: Evidence that signaling endosomes serve as a platform for the Ras-MAPK pathway
NGF signaling from clathrin-coated vesicles: Evidence that signaling endosomes serve as a platform for the Ras-MAPK pathway
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DOI：
10.1016/s0896-6273(01)00526-8
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发表时间：
2001-12-06
期刊：
影响因子：
16.2
通讯作者：
Mobley, WC
中科院分区：
文献类型：
--
作者：
Howe, CL;Valletta, JS;Mobley, WC
靶源性神经营养因子“神经生长因子”（NGF）通过TrkA发出信号以促进神经元的存活、分化和维持。轴突末梢中的NGF信号如何传递到细胞体尚不清楚。“信号内体假说”设想NGF-TrkA复合物在轴突末端内化并逆行转运至细胞体。在NGF处理后，我们发现网格蛋白包被的囊泡含有与TrkA结合的NGF以及Ras-MAP激酶途径的活化信号蛋白。这些囊泡可以发出信号的证据是它们在体外激活Erk 1/2下游靶点Elk的能力。我们的研究结果表明，在神经生长因子处理的细胞中，存在一群来自网格蛋白包被膜的信号内体。
The target-derived neurotrophic factor "nerve growth factor" (NGF) signals through TrkA to promote the survival, differentiation, and maintenance of neurons. How the NGF signal in axon terminals is conveyed to the cell body is unknown. The "signaling endosome hypothesis" envisions that NGF-TrkA complexes are internalized at the axon terminal and retrogradely transported to the cell body. Following NGF treatment, we found that clathrin-coated vesicles contained NGF bound to TrkA together with activated signaling proteins of the Ras-MAP kinase pathway. Evidence that these vesicles could signal was their ability in vitro to activate Elk, a downstream target of Erk1/2. Our results point to the existence of a population of signaling endosomes derived from clathrin-coated membranes in NGF-treated cells.