GTP hydrolysis of TC10 promotes neurite outgrowth through exocytic fusion of Rab11- and L1-containing vesicles by releasing exocyst component Exo70.
GTP hydrolysis of TC10 promotes neurite outgrowth through exocytic fusion of Rab11- and L1-containing vesicles by releasing exocyst component Exo70.
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DOI：
10.1371/journal.pone.0079689
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Nakamura T
中科院分区：
文献类型：
--
作者：
Fujita A;Koinuma S;Yasuda S;Nagai H;Kamiguchi H;Wada N;Nakamura T
利用胞吐作用使神经生长锥的膜扩张对于神经突的生长至关重要。TC 10是Rho家族的一种GTP酶，对于特定类型的囊泡向质膜的运输至关重要。最近的研究表明，TC10及其效应器Exo70，外囊栓系复合物的一个组成部分，有助于神经突生长。然而，TC10促进神经发生功能的分子机制仍有待建立。在这里，我们提出，GTP水解的囊泡TC10质膜附近促进神经突生长，通过释放Exo70加速囊泡融合。使用Förster共振能量转移（FRET）为基础的生物传感器，我们表明，TC10的活性在质膜下降，在海马神经元和神经生长因子（NGF）处理的PC12细胞的生长锥延伸。在神经元细胞中，TC10在囊泡的活性高于其在质膜的活性，并且发现TC10阳性囊泡在NGF处理的PC12细胞中融合到质膜。因此，推测TC10在囊泡处的活性在神经元胞吐期间在质膜附近失活。我们的模型得到功能证据的支持，即组成型活性TC10不能挽救减少由TC10耗尽引起的NGF诱导的神经突生长。此外，TC10敲除实验和共定位分析证实了Exo70参与TC10介导的神经元细胞运输。TC10经常驻留在含有Rab11的囊泡上，Rab11是再循环途径的关键调节剂，并与神经突生长有关。在生长锥中，大多数含有细胞粘附分子L1的囊泡具有TC10。Rab11和L1阳性囊泡的胞吐作用可能在TC10介导的神经突生长中发挥核心作用。结合本研究和我们以前的工作，在EGF诱导的HeLa细胞胞吐作用的TC10的作用表明，这里提出的含有TC10的信号机制可能被广泛用于胞吐。
The use of exocytosis for membrane expansion at nerve growth cones is critical for neurite outgrowth. TC10 is a Rho family GTPase that is essential for specific types of vesicular trafficking to the plasma membrane. Recent studies have shown that TC10 and its effector Exo70, a component of the exocyst tethering complex, contribute to neurite outgrowth. However, the molecular mechanisms of the neuritogenesis-promoting functions of TC10 remain to be established. Here, we propose that GTP hydrolysis of vesicular TC10 near the plasma membrane promotes neurite outgrowth by accelerating vesicle fusion by releasing Exo70. Using Förster resonance energy transfer (FRET)-based biosensors, we show that TC10 activity at the plasma membrane decreased at extending growth cones in hippocampal neurons and nerve growth factor (NGF)-treated PC12 cells. In neuronal cells, TC10 activity at vesicles was higher than its activity at the plasma membrane, and TC10-positive vesicles were found to fuse to the plasma membrane in NGF-treated PC12 cells. Therefore, activity of TC10 at vesicles is presumed to be inactivated near the plasma membrane during neuronal exocytosis. Our model is supported by functional evidence that constitutively active TC10 could not rescue decrease in NGF-induced neurite outgrowth induced by TC10 depletion. Furthermore, TC10 knockdown experiments and colocalization analyses confirmed the involvement of Exo70 in TC10-mediated trafficking in neuronal cells. TC10 frequently resided on vesicles containing Rab11, which is a key regulator of recycling pathways and implicated in neurite outgrowth. In growth cones, most of the vesicles containing the cell adhesion molecule L1 had TC10. Exocytosis of Rab11- and L1-positive vesicles may play a central role in TC10-mediated neurite outgrowth. The combination of this study and our previous work on the role of TC10 in EGF-induced exocytosis in HeLa cells suggests that the signaling machinery containing TC10 proposed here may be broadly used for exocytosis.
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DOI：
10.1523/jneurosci.3907-09.2009
发表时间：
2009-10-21
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Dupraz S;Grassi D;Bernis ME;Sosa L;Bisbal M;Gastaldi L;Jausoro I;Cáceres A;Pfenninger KH;Quiroga S
通讯作者：
Quiroga S
影响因子：
5.3
作者：
Bodrikov, Vsevolod;Solis, Gonzalo P.;Stuermer, Claudia A. O.
通讯作者：
Stuermer, Claudia A. O.
依赖Ship2的负反馈回路在神经生长因子刺激的PC12细胞的神经发生中的重要作用。
影响因子：
7.8
作者：
Aoki, Kazuhiro;Nakamura, Takeshi;Inoue, Takanari;Meyer, Tobias;Matsuda, Michiyuki
通讯作者：
Matsuda, Michiyuki
DOI：
10.1111/j.1600-0854.2012.01353.x
发表时间：
2012-07
期刊：
Traffic (Copenhagen, Denmark)
影响因子：
--
作者：
Heider MR;Munson M
通讯作者：
Munson M
影响因子：
5.3
作者：
Cuadra, AE;Kuo, SH;Chetkovich, DM
通讯作者：
Chetkovich, DM