Pincher, a pinocytic chaperone for nerve growth factor/TrkA signaling endosomes.
Pincher, a pinocytic chaperone for nerve growth factor/TrkA signaling endosomes.
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Pincher，一种用于神经生长因子/TRKA信号内体的皮细胞伴侣。
DOI：
10.1083/jcb.200201063
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发表时间：
2002-05-13
影响因子：
7.8
通讯作者：
Halegoua, Simon
中科院分区：
文献类型：
--
作者：
Shao, Yufang;Akmentin, Wendy;Toledo-Aral, Juan Jose;Rosenbaum, Julie;Valdez, Gregorio;Cabot, John B;Hilbush, Brian S;Halegoua, Simon
神经生长因子（NGF）作用的中心原则是其通过受体TrkA介导细胞质信号的能力，该信号在神经末梢启动并传递到体细胞。我们发现了一种NGF诱导的蛋白，我们将其命名为Pincher (pinocytic chaperone)，它介导NGF及其受体TrkA的内吞和运输。在PC12细胞中，Pincher的过表达显著刺激了ngf诱导的TrkA内吞作用，出乎意料地出现在细胞表面褶边中不依赖网格蛋白的巨噬细胞作用位点。随后，一个含有pincher的小管系统介导了含有NGF/ trka的小泡向细胞质聚积的传递。这些囊泡选择性和持续性地介导TrkA-erk5丝裂原激活的蛋白激酶信号。Pincher的显性抑制性突变形式抑制ngf诱导的TrkA内吞作用，并选择性阻断TrkA介导的erk5细胞质信号传导，而不是erk1/2激酶。我们的研究结果表明Pincher介导功能特化的NGF/TrkA内体的胞吞作用，具有持续的信号传导潜力。
Acentral tenet of nerve growth factor (NGF) action that is poorly understood is its ability to mediate cytoplasmic signaling, through its receptor TrkA, that is initiated at the nerve terminal and conveyed to the soma. We identified an NGF-induced protein that we termed Pincher (pinocytic chaperone) that mediates endocytosis and trafficking of NGF and its receptor TrkA. In PC12 cells, overexpression of Pincher dramatically stimulated NGF-induced endocytosis of TrkA, unexpectedly at sites of clathrin-independent macropinocytosis within cell surface ruffles. Subsequently, a system of Pincher-containing tubules mediated the delivery of NGF/TrkA-containing vesicles to cytoplasmic accumulations. These vesicles selectively and persistently mediated TrkA-erk5 mitogen-activated protein kinase signaling. A dominant inhibitory mutant form of Pincher inhibited the NGF-induced endocytosis of TrkA, and selectively blocked TrkA-mediated cytoplasmic signaling of erk5, but not erk1/2, kinases. Our results indicate that Pincher mediates pinocytic endocytosis of functionally specialized NGF/TrkA endosomes with persistent signaling potential.