Molecular mechanisms for LPA_3-mediated neurite branch formation

LPA_3介导的神经突分支形成的分子机制

• 批准号: 21590109
• 负责人: FUKUSHIMA Nobuyuki
• 金额: $ 3万
• 依托单位: Kinki University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21590109/
• 关键词: リゾホスファチジン酸; G蛋白質; 神経軸索; 分岐; 神経ネットワーク; LPA3; 神経分岐; Rnd2; リゾホスファジン酸

Although neurite branching is crucial for neuronal network formation after birth, its underlying mechanisms remain unclear. Here, we demonstrate that lysophosphatidic acid(LPA) stimulates neurite branching through a novel signaling pathway. Treatment of neuronal cell lines with LPA resulted in neurite branch formation when LPA_3 receptor was introduced. The effects of LPA were blocked by inhibition of G_q signaling. Furthermore, expression of inhibitory mutants of the small GTPase Rnd2/Rho7 or an Rnd2 effector rapostlin abolished LPA_3-mediated neurite branching. The LPA_3 agonist 2(S)-OMPT or LPA also induced axonal branch formation in hippocampal neurons, which was blocked by G_q and Rnd2 pathway inhibition or LPA_3 knockdown. These findings suggest that the novel signaling pathway involving LPA_3, G_q, and Rnd2 may play an important role in neuronal network formation.

虽然轴突分支对于出生后神经元网络的形成是至关重要的，但其潜在的机制仍不清楚。在这里，我们证明了溶血磷脂酸(LPA)通过一种新的信号通路刺激轴突分支。当LPA_3受体被引入时，LPA处理神经细胞系可引起轴突分支形成。LPA的作用可通过抑制G_q信号而被阻断。此外，表达小GTP酶Rnd2/Rho7的抑制性突变体或Rnd2效应突变体rapostlin可阻断LPA_3介导的轴突分支。LPA_3激动剂2(S)-OMPT或LPA也可诱导海马神经元形成轴突，该作用可被G_q和RND2通路抑制或LPA_3基因敲除所阻断。这些发现提示，LPA_3、G_q和RND2参与的信号通路可能在神经元网络的形成中发挥重要作用。

项目成果

Regulation of neurite morphology by LPA

LPA 对神经突形态的调节

• 发表时间: 2009
• 作者: 寺井易子;河原知世;木戸悠佳;深川愛未;松浦未工;宮本優里;松尾剛明;西田健太朗;長澤一樹;Fukushima Nobuyuki
• 通讯作者: Fukushima Nobuyuki

Induction of lysophosphatidic acid receptor-3 by 12-O-tetradecanoylphorbol-13-acetate stimulates cell migration of rat liver cells

• DOI: 10.1016/j.canlet.2011.06.020
• 发表时间: 2011-10-28
• 期刊: CANCER LETTERS
• 影响因子: 9.7
• 作者: Okabe, Kyoko;Kato, Kohei;Tsujiuchi, Toshifumi
• 通讯作者: Tsujiuchi, Toshifumi

Coordinated interactions between actin and microtubules through crosslinkers in neurite retraction induced by lysophosphatidic acid

• DOI: 10.1016/j.neuint.2011.04.020
• 发表时间: 2011-08-01
• 期刊: NEUROCHEMISTRY INTERNATIONAL
• 影响因子: 4.2
• 作者: Fukushima, Nobuyuki;Furuta, Daisuke;Tsujiuchi, Toshifumi
• 通讯作者: Tsujiuchi, Toshifumi

Cytoskeleton of the nervous system. Series : Advances in Neurobiology

神经系统的细胞骨架。

• 发表时间: 2011
• 作者: Fukushima;N.
• 通讯作者: N.

Lysophosphatidic acid influences initial neuronal polarity establishment

• DOI: 10.1016/j.neulet.2010.06.031
• 发表时间: 2010-08-16
• 期刊: NEUROSCIENCE LETTERS
• 影响因子: 2.5
• 作者: Yamane, Masayuki;Furuta, Daisuke;Fukushima, Nobuyuki
• 通讯作者: Fukushima, Nobuyuki