LPA4/p2y9/GPR23 Mediates Rho-dependent Morphological Changes in a Rat Neuronal Cell Line*
LPA4/p2y9/GPR23 Mediates Rho-dependent Morphological Changes in a Rat Neuronal Cell Line*
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DOI：
10.1074/jbc.m610767200
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发表时间：
2007-02
影响因子：
4.8
通讯作者：
K. Yanagida;S. Ishii;F. Hamano;K. Noguchi;Takao Shimizu
中科院分区：
文献类型：
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作者：
K. Yanagida;S. Ishii;F. Hamano;K. Noguchi;Takao Shimizu
溶血磷脂酸 (LPA) 是一种有效的脂质介质，可通过其特定的 G 蛋白偶联受体在许多细胞类型中引发多种生物反应。特别是，LPA 影响神经元细胞的细胞形态、细胞存活和细胞周期进程。最近，我们将 p2y9/GPR23 鉴定为新的第四种 LPA 受体 LPA4（Noguchi, K.、Ishii, S. 和 Shimizu, T. (2003) J. Biol. Chem. 278, 25600-25606）。为了评估 LPA4 在神经元细胞中的功能，我们使用了缺乏对 LPA 内源性反应的大鼠神经母细胞瘤 B103 细胞。在稳定表达 LPA4 的 B103 细胞中，我们观察到 Gq/11 依赖性钙动员，但 LPA 不影响腺苷酸环化酶活性。在 LPA4 转染子中，LPA 诱导显着的形态变化，即神经突收缩、细胞聚集和钙粘蛋白依赖性细胞粘附，这些变化涉及 Rho 介导的信号通路。因此，我们的结果表明，LPA4 以及 LPA1 与 Gq/11 和 G12/13 偶联，而 LPA4 与 LPA1 的不同之处在于它不与 Gi/o 偶联。通过神经突回缩和细胞聚集，LPA4 可能在神经发生和神经元迁移等神经元发育中发挥作用。
Lysophosphatidic acid (LPA) is a potent lipid mediator that evokes a variety of biological responses in many cell types via its specific G protein-coupled receptors. In particular, LPA affects cell morphology, cell survival, and cell cycle progression in neuronal cells. Recently, we identified p2y9/GPR23 as a novel fourth LPA receptor, LPA4 (Noguchi, K., Ishii, S., and Shimizu, T. (2003) J. Biol. Chem. 278, 25600-25606). To assess the functions of LPA4 in neuronal cells, we used rat neuroblastoma B103 cells that lack endogenous responses to LPA. In B103 cells stably expressing LPA4, we observed Gq/11-dependent calcium mobilization, but LPA did not affect adenylyl cyclase activity. In LPA4 transfectants, LPA induced dramatic morphological changes, i.e. neurite retraction, cell aggregation, and cadherin-dependent cell adhesion, which involved Rho-mediated signaling pathways. Thus, our results demonstrated that LPA4 as well as LPA1 couple to Gq/11 and G12/13, whereas LPA4 differs from LPA1 in that it does not couple to Gi/o. Through neurite retraction and cell aggregation, LPA4 may play a role in neuronal development such as neurogenesis and neuronal migration.