Rho family GTPases and neuronal growth cone remodelling: Relationship between increased complexity induced by Cdc42Hs, Rac1, and acetylcholine and collapse induced by RhoA and lysophosphatidic acid
Rho family GTPases and neuronal growth cone remodelling: Relationship between increased complexity induced by Cdc42Hs, Rac1, and acetylcholine and collapse induced by RhoA and lysophosphatidic acid
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DOI：
10.1128/mcb.17.3.1201
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发表时间：
1997-03-01
影响因子：
5.3
通讯作者：
Lim, L
中科院分区：
文献类型：
--
作者：
Kozma, R;Sarner, S;Lim, L
Rho 家族 GTP 酶在非神经元细胞中基于肌动蛋白的形态的形成中发挥着重要作用，在此我们表明，显微注射 Cdc42Hs 和 Rad 促进了 N1E-115 神经母细胞瘤生长锥和沿神经突的丝状伪足和板状伪足的形成。这些含有肌动蛋白的结构也可以通过注射肉毒杆菌C3外切酶来诱导，从而消除了RhoA介导的功能，例如神经突收缩。与显性失活突变体CdC42Hs(T17N)共注射可以抑制C3反应，而与RhoA共注射可以竞争Cdc42Hs反应。我们还证明，神经递质乙酰胆碱 (ACh) 可以通过毒蕈碱 ACh 受体激活在神经母细胞瘤生长锥上诱导丝状伪足和片状伪足，但仅限于以浓度梯度应用时。分别预注射显性失活突变体 CdC42Hs(T17N) 和 Rac1(T17N) 可以抑制 ACh 诱导的丝状伪足和片状伪足的形成。由 RhoA 介导的溶血磷脂酸 (LPA) 诱导的神经突回缩可被 ACh 抑制，而注射 CdC42Hs(T17N) 或 Rac1(T17N) 可抑制 C3 外切酶介导的神经突生长。这些结果共同表明，由 Cdc42Hs 和/或 Rad 以及 RhoA 介导的 ACh 和 LPA 诱导的形态途径之间存在竞争，导致神经突发育或塌陷。
Rho family GTPases have been assigned important roles in the formation of actin-based morphologies in nonneuronal cells, Here we show that microinjection of Cdc42Hs and Rad promoted formation of filopodia and lamellipodia in N1E-115 neuroblastoma growth cones and along neurites. These actin-containing structures were also induced by injection of Clostridium botulinum C3 exoenzyme, which abolishes RhoA-mediated functions such as neurite retraction, The C3 response was inhibited by coinjection with the dominant negative mutant CdC42Hs(T17N), while the Cdc42Hs response could be competed by coinjection with RhoA. We also demonstrate that the neurotransmitter acetylcholine (ACh) can induce filopodia and lamellipodia on neuroblastoma growth cones via muscarinic ACh receptor activation, but only when applied in a concentration gradient. ACh-induced formation of filopodia and lamellipodia was inhibited by preinjection with the dominant negative mutants CdC42Hs(T17N) and Rac1(T17N) respectively. Lysophosphatidic acid (LPA)-induced neurite retraction, which is mediated by RhoA, was inhibited by ACh, while C3 exoenzyme-mediated neurite outgrowth was inhibited by injection with CdC42Hs(T17N) or Rac1(T17N). Together these results suggest that there is competition between the ACh- and LPA-induced morphological pathways mediated by Cdc42Hs and/or Rad and by RhoA, leading to either neurite development or collapse.