Collapsin response mediator protein-2 regulates neurite formation by modulating tubulin GTPase activity
Collapsin response mediator protein-2 regulates neurite formation by modulating tubulin GTPase activity
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DOI：
10.1016/j.cellsig.2009.07.017
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发表时间：
2009-12-01
影响因子：
4.8
通讯作者：
Ryu, Sung Ho
中科院分区：
文献类型：
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作者：
Chae, Young Chan;Lee, Sukmook;Ryu, Sung Ho
坍缩反应介质蛋白-2 （CRMP-2）通过调节微管动力学在轴突发育中起关键作用。然而，这一功能背后的分子机制尚未被清楚地阐明。在这项研究中，我们证明了hCRMP-2，特别是氨基酸残基480-509，是刺激微管蛋白GTPase活性所必需的。我们还发现hCRMP-2的gtpase激活蛋白（GAP）活性对分化的PC12嗜铬细胞瘤细胞系的微管组装和神经突形成很重要。突变体hCRMP-2缺乏负责GAP活性的精氨酸残基，抑制微管组装和神经突形成。有趣的是，我们发现hCRMP-2的n端区域（氨基酸150-299）通过与c端区域（氨基酸480-509）的直接相互作用对GAP活性具有抑制作用。我们的研究结果表明，CRMP-2作为微管蛋白的直接结合物可能是神经突形成过程中微管蛋白的GAP，其CAP活性可能通过与n端抑制区域的分子内相互作用来调节。(C) 2009爱思唯尔公司版权所有。
Collapsin response mediator protein-2 (CRMP-2) plays a key role in axonal development by regulating microtubule dynamics. However, the molecular mechanisms underlying this function have not been clearly elucidated. In this study, we demonstrated that hCRMP-2, specifically amino acid residues 480-509, is essential for stimulating tubulin GTPase activity. We also found that the GTPase-activating protein (GAP) activity of hCRMP-2 was important for microtubule assembly and neurite formation in differentiated PC12 pheochromocytoma cell lines. Mutant hCRMP-2, lacking arginine residues responsible for GAP activity, inhibited microtubule assembly and neurite formation. Interestingly, we found that the N-terminal region (amino acids 150-299) of hCRMP-2 had an inhibitory role on GAP activity via a direct interaction with the C-terminal region (amino acids 480-509). Our results suggest that CRMP-2 as a tubulin direct binder may be a GAP of tubulin in neurite formation and that its CAP activity may be regulated by an intramolecular interaction with an N-terminal inhibitory region. (C) 2009 Elsevier Inc. All rights reserved.