Expression and function of neuronal growth-associated proteins (nGAPs) in PC12 cells
Expression and function of neuronal growth-associated proteins (nGAPs) in PC12 cells
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DOI：
10.1016/j.neures.2011.01.006
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发表时间：
2011-05-01
影响因子：
2.9
通讯作者：
Igarashi, Michihiro
中科院分区：
文献类型：
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作者：
Lu, Jia;Nozumi, Motohiro;Igarashi, Michihiro
生长锥在神经连接、突触形成和轴突再生中起着至关重要的作用。细胞骨架元件的持续重排和将囊泡运输到质膜上是生长锥运动所必需的；然而，直接参与这些过程的蛋白质及其特定功能尚未很好地确定。我们最近确定了17种蛋白质作为哺乳动物生长锥的功能标记蛋白和大鼠皮质神经元中的神经元生长相关蛋白(nGAPs；Nozumi等人，2009)。为了确定这17个蛋白是否是其他神经细胞类型中的生长锥标记，我们检测了它们在PC12D细胞中的表达和功能。我们发现，所有17个nGAP都高度集中在PC12D细胞的生长锥中，并且RNAi将它们全部敲除后，减少或抑制了突起的生长，这表明所有17个nGAP都可能是通用的生长锥标记。其中，有8种蛋白质可以调节PC12D生长锥体中F-肌动蛋白的含量。其中两个nGAP是细胞骨架蛋白。Cap1和Sept2通过调节F-肌动蛋白的含量增加了平均生长锥面积和平均轴突长度，Sept2还促进了丝状突起的生长。综上所述，我们的数据表明，一些nGAP是多种神经细胞类型中生长锥的通用标记，其中一些，如Cap1和Sept2，通过F-肌动蛋白的重排来调节生长锥的形态，从而控制轴突的生长。(C)2011年爱思唯尔爱尔兰有限公司和日本神经科学学会。版权所有。
The growth cone plays crucial roles in neural wiring, synapse formation, and axonal regeneration. Continuous rearrangement of cytoskeletal elements and targeting of transported vesicles to the plasma membrane are essential to growth cone motility; however, the proteins directly involved in these processes and their specific functions are not well established. We recently identified 17 proteins as functional marker proteins of the mammalian growth cone and as neuronal growth-associated proteins in rat cortical neurons (nGAPs; Nozumi et al., 2009). To determine whether these 17 proteins are growth cone markers in other neuronal cell types, we examined their expression and function in PC12D cells. We found that all 17 nGAPs were highly concentrated in the growth cones of PC12D cells, and that knockdown of all of them by RNAi reduced or inhibited neurite outgrowth, indicating that all of the 17 nGAPs may be general growth cone markers. Among them, eight proteins were shown to regulate the amount of F-actin in PC12D growth cones. Two of these nGAP that are cytoskeletal proteins. Cap1 and Sept2, increased the mean growth cone area and the mean neurite length by regulating the amount of F-actin; Sept2 also induced filopodial growth. Taken together, our data suggested that some of the nGAPs were generalized markers of the growth cone in multiple neuronal cell types and some of them, such as Cap1 and Sept2, regulated growth cone morphology through rearrangement of F-actin and thereby controlled neurite outgrowth. (C) 2011 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.