Local translation of TC10 is required for membrane expansion during axon outgrowth.

Local translation of TC10 is required for membrane expansion during axon outgrowth.
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DOI:
10.1038/ncomms4506
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发表时间:
2014-03-25
影响因子:
16.6
通讯作者:
Hengst, Ulrich
Hengst, Ulrich
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Gracias, Neilia G.;Shirkey-Son, Nicole J.;Hengst, Ulrich

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发育中的轴突表面在由外囊复合物介导的过程中扩张。外囊的时空调节只是部分了解。在这里,我们报告说,刺激膜扩大背根神经节(DRG)轴突是由轴突内合成的TC 10,一个小的GT 10所需的外囊功能。诱导膜扩张和轴突生长的抑制后,轴突特异性敲低TC 10 mRNA。为了确定轴突内TC 10合成与先前描述的刺激诱导的翻译的细胞骨架调节器Par 3的关系,我们调查的信号通路控制其本地翻译响应于NGF。Rheb-mTOR通路的磷酸肌醇3-激酶(PI 3 K)依赖性激活触发TC 10和Par 3的同时局部合成。这些结果揭示了膜动力学控制中的本地翻译的重要性,并表明本地化的mTOR依赖性蛋白质合成触发并行途径的同时激活。
The surface of developing axons expands in a process mediated by the exocyst complex. The spatial-temporal regulation of the exocyst is only partially understood. Here we report that stimulated membrane enlargement in dorsal root ganglion (DRG) axons is triggered by intra-axonal synthesis of TC10, a small GTPase required for exocyst function. Induced membrane expansion and axon outgrowth are inhibited after axon-specific knockdown of TC10 mRNA. To determine the relationship of intra-axonal TC10 synthesis with the previously described stimulus-induced translation of the cytoskeletal regulator Par3, we investigate the signaling pathways controlling their local translation in response to NGF. Phosphoinositide 3-kinase (PI3K)-dependent activation of the Rheb-mTOR pathway triggers the simultaneous local synthesis of TC10 and Par3. These results reveal the importance of local translation in the control of membrane dynamics and demonstrate that localized, mTOR-dependent protein synthesis triggers the simultaneous activation of parallel pathways.
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