The TC10-Exo70 complex is essential for membrane expansion and axonal specification in developing neurons.
The TC10-Exo70 complex is essential for membrane expansion and axonal specification in developing neurons.
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DOI：
10.1523/jneurosci.3907-09.2009
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发表时间：
2009-10-21
期刊：
影响因子：
--
通讯作者：
Quiroga S
中科院分区：
文献类型：
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作者：
Dupraz S;Grassi D;Bernis ME;Sosa L;Bisbal M;Gastaldi L;Jausoro I;Cáceres A;Pfenninger KH;Quiroga S
轴突伸长是神经元极化的标志之一。这种现象需要轴突膜生长的质膜前体囊泡（PPV）的胞吐作用在神经生长锥，由IGF-1激活的PI 3 k途径调节的过程。然而，有关PPV的靶向机制的细节知之甚少。在这里，我们表明，在培养的海马锥体神经元和生长锥分离胎鼠脑，IGF-1激活GTP结合蛋白TC 10，触发易位到质膜的exocyst组件exo 70在远端轴突和生长锥。我们还表明，TC 10和exo 70的功能是必要的添加新的膜，因此，轴突伸长IGF-1刺激。此外，TC 10或exo 70的表达沉默通过阻碍IGF-1受体插入未分化的神经突中来抑制神经元极性的建立。我们的结论是，在培养的海马锥体神经元中，（i）轴突生长锥处的膜扩张由IGF-1通过涉及TC 10和外囊复合物的级联调节，（ii）TC 10和exo 70对于IGF-1受体的极化外化是必不可少的，并且（iii）这个过程对于轴突特异化是必要的。
Axonal elongation is one of the hallmarks of neuronal polarization. This phenomenon requires axonal membrane growth by exocytosis of plasmalemmal precursor vesicles (PPVs) at the nerve growth cone, a process regulated by IGF-1 activation of the PI3k pathway. Few details are known, however, about the targeting mechanisms for PPVs. Here we show, in cultured hippocampal pyramidal neurons and growth cones isolated from fetal rat brain, that IGF-1 activates the GTP-binding protein TC10, which triggers translocation to the plasma membrane of the exocyst component exo70 in the distal axon and growth cone. We also show that TC10 and exo70 function are necessary for addition of new membrane and, thus, axon elongation stimulated by IGF-1. Moreover, expression silencing of either TC10 or exo70 inhibit the establishment of neuronal polarity by hindering the insertion of IGF-1 receptor in one of the undifferentiated neurites. We conclude that, in hippocampal pyramidal neurons in culture, (i) membrane expansion at the axonal growth cone is regulated by IGF-1 via a cascade involving TC10 and the exocyst complex, (ii) TC10 and exo70 are essential for the polarized externalization of IGF-1 receptor, and (iii) this process is necessary for axon specification.