Ventricular zone gene-1 (vzg-1) encodes a lysophosphatidic acid receptor expressed in neurogenic regions of the developing cerebral cortex.
Ventricular zone gene-1 (vzg-1) encodes a lysophosphatidic acid receptor expressed in neurogenic regions of the developing cerebral cortex.
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DOI：
10.1083/jcb.135.4.1071
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发表时间：
1996-11
期刊：
影响因子：
--
通讯作者：
Chun J
中科院分区：
文献类型：
--
作者：
Hecht JH;Weiner JA;Post SR;Chun J
本研究利用新皮质神经母细胞系克隆G蛋白偶联受体（GPCR）基因，以研究调控皮质神经发生的信号机制。一个假定的GPCR基因显示在皮质神经原性区域的原位表达模式，因此被命名为心室区基因-1（vzg-1）。vzg-1 cDNA与3.8kb的mRNA转录本杂交，并编码预测分子量为41-42 kD的蛋白质，经Western印迹分析证实。为了评估其功能，vzg-1在克隆它的细胞系中过表达，诱导血清依赖性“细胞变圆”。溶血磷脂酸（LPA）是一种高浓度存在于血清中的生物活性脂质，重现了单独使用血清时所观察到的效果。在vzg-1过表达细胞中未观察到对其他相关磷脂或凝血酶（另一种通过GPCR诱导细胞变圆的试剂）的形态学反应。Vzg-1过表达降低了LPA对细胞变圆和Gi激活的EC 50。百日咳毒素处理抑制vzg-1依赖性LPA介导的Gi活化，但对细胞变圆没有影响。膜结合研究表明，vzg-1过表达增加特异性LPA结合。这些分析鉴定了vzg-1基因产物作为LPA的受体，表明LPA信号传导机制在皮质神经发生中的作用。因此，Vzg-1通过单一受体提供了细胞外LPA和LPA介导的信号传导途径的激活之间的联系，并将允许对神经和非神经系统中的LPA信号传导进行新的研究。
Neocortical neuroblast cell lines were used to clone G-protein-coupled receptor (GPCR) genes to study signaling mechanisms regulating cortical neurogenesis. One putative GPCR gene displayed an in situ expression pattern enriched in cortical neurogenic regions and was therefore named ventricular zone gene-1 (vzg-1). The vzg-1 cDNA hybridized to a 3.8-kb mRNA transcript and encoded a protein with a predicted molecular mass of 41-42 kD, confirmed by Western blot analysis. To assess its function, vzg-1 was overexpressed in a cell line from which it was cloned, inducing serum-dependent "cell rounding." Lysophosphatidic acid (LPA), a bioactive lipid present in high concentrations in serum, reproduced the effect seen with serum alone. Morphological responses to other related phospholipids or to thrombin, another agent that induces cell rounding through a GPCR, were not observed in vzg-1 overexpressing cells. Vzg-1 overexpression decreased the EC50 of both cell rounding and Gi activation in response to LPA. Pertussis toxin treatment inhibited vzg-1-dependent LPA-mediated Gi activation, but had no effect on cell rounding. Membrane binding studies indicated that vzg-1 overexpression increased specific LPA binding. These analyses identify the vzg-1 gene product as a receptor for LPA, suggesting the operation of LPA signaling mechanisms in cortical neurogenesis. Vzg-1 therefore provides a link between extracellular LPA and the activation of LPA- mediated signaling pathways through a single receptor and will allow new investigations into LPA signaling both in neural and nonneural systems.