Interaction of Mint2 with TrkA Is Involved in Regulation of Nerve Growth Factor-induced Neurite Outgrowth*
Interaction of Mint2 with TrkA Is Involved in Regulation of Nerve Growth Factor-induced Neurite Outgrowth*
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DOI：
10.1074/jbc.m809214200
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发表时间：
2009-05
影响因子：
4.8
通讯作者：
Yong Zhang;Yong-Gang Wang;Qi Zhang;Xiujie Liu;Xuan Liu;Li Jiao;Wei Zhu;Zhao-Huan Zhang
中科院分区：
文献类型：
--
作者：
Yong Zhang;Yong-Gang Wang;Qi Zhang;Xiujie Liu;Xuan Liu;Li Jiao;Wei Zhu;Zhao-Huan Zhang
TrkA 受体信号传导对于神经生长因子 (NGF) 诱导的感觉神经元的存活和分化至关重要。为了鉴定 TrkA 信号传导的可能效应子或调节子，使用 TrkA 的胞内结构域作为诱饵进行酵母双杂交筛选。我们将 muc18-1 相互作用蛋白 2 (Mint2) 鉴定为一种新型 TrkA 结合蛋白，并发现 Mint2 的磷酸酪氨酸结合域以不依赖于磷酸化和配体的方式与 TrkA 相互作用。免疫共沉淀分析表明，内源性 TrkA 与大鼠组织匀浆中的 Mint2 相互作用，免疫组织化学证据表明 Mint2 和 TrkA 在大鼠背根神经节神经元中共定位。此外，Mint2过表达抑制了PC12和培养的背根神经节神经元中NGF诱导的神经突生长，而通过RNA干扰抑制Mint2表达则促进了NGF诱导的神经突生长。此外，Mint2被发现可以促进TrkA在高尔基体中的保留并抑制其表面分选。总而言之，我们的数据提供证据表明 Mint2 是一种新型 TrkA 调节蛋白，它可能通过涉及 TrkA 在高尔基体中保留的机制影响 NGF 诱导的神经突生长。
TrkA receptor signaling is essential for nerve growth factor (NGF)-induced survival and differentiation of sensory neurons. To identify possible effectors or regulators of TrkA signaling, yeast two-hybrid screening was performed using the intracellular domain of TrkA as bait. We identified muc18-1-interacting protein 2 (Mint2) as a novel TrkA-binding protein and found that the phosphotyrosine binding domain of Mint2 interacted with TrkA in a phosphorylation- and ligand-independent fashion. Coimmunoprecipitation assays showed that endogenous TrkA interacted with Mint2 in rat tissue homogenates, and immunohistochemical evidence revealed that Mint2 and TrkA colocalized in rat dorsal root ganglion neurons. Furthermore, Mint2 overexpression inhibited NGF-induced neurite outgrowth in both PC12 and cultured dorsal root ganglion neurons, whereas inhibition of Mint2 expression by RNA interference facilitated NGF-induced neurite outgrowth. Moreover, Mint2 was found to promote the retention of TrkA in the Golgi apparatus and inhibit its surface sorting. Taken together, our data provide evidence that Mint2 is a novel TrkA-regulating protein that affects NGF-induced neurite outgrowth, possibly through a mechanism involving retention of TrkA in the Golgi apparatus.