Biological activity of neurotrophins is dependent on recruitment of Rac1 to lipid rafts
Biological activity of neurotrophins is dependent on recruitment of Rac1 to lipid rafts
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DOI：
10.1016/j.bbrc.2004.11.151
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发表时间：
2005-02-04
影响因子：
3.1
通讯作者：
Yamashita, T
中科院分区：
文献类型：
--
作者：
Fujitani, M;Honda, A;Yamashita, T
Rho家族是真核细胞中肌动蛋白细胞骨架的关键调节因子，参与了神经元形态的调控。在这里，我们报告了海马神经元或PC12细胞中神经营养素依赖的细胞骨架改变，这是rac1表型的特征，被脂筏完整性的破坏所抑制。在胆固醇耗竭的PC12细胞中，NGF诱导的rac1的激活受到损害。用GammaGTP预处理后，可能以GTP结合的形式将大量的rac1从非RAFT组分转移到RAFT组分。在确定神经营养因子的生物活性时，适当地将激活的rac1重新招募到脂筏(代表特殊信号细胞器的结构)中是至关重要的。(C)2004 Elsevier Inc.保留所有权利。
The Rho family of small GTPases, key regulators of the actin cytoskeleton in eukaryotic cells, is implicated in the control of neuronal morphology. Here, we report that neurotrophin dependent cytoskeletal changes, characteristic of the phenotype of Rac1, in the hippocampal neurons or PC12 cells are inhibited by the disruption of lipid raft integrity. Activation of Rac1 induced by NGF is impaired in cholesterol-depleted PC12 cells. Pretreatment with gammaGTP shifted significant amount of Rac1, presumably in a GTP-bound form, from non-raft to raft fractions. Proper recruitment of activated Rac1 to lipid rafts, structures that represent specialized signaling organelles, is of fundamental importance in determining neurotrophins' bioactivity. (C) 2004 Elsevier Inc. All rights reserved.