STUDY ON FUNCTION OF PHOSPHOLIPASE D2 IN NEURITE REMODELING

磷脂酶D2在神经突重塑中的作用研究

基本信息

批准号：
14380310
负责人：
KANAHO Yasunori
金额：
$ 9.54万
依托单位：
TOKYO METROPOLITAN ORGANIZATION FOR MEDICAL RESEARCH
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2003
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14380310/
关键词：
Phospholipase D Neurite ERK PC 12 cells Cerebellar granule cells NGF Neuronal adhesion molecule Signal transduction 小脳顆粒細胞軸索伸長神経細胞接着分子一級アルコール

项目摘要

Mammalian phospholipase D (PLD) is a novel signal transducing enzyme, which is believed to play roles in a wide variety of cell functions. Two mammalian PLD isozymes, PLD1 and PLD2,have been identified. Although activation mechanisms and physiological functions of PLD1 have been well documented, those of PLD2 still remain to be clarified. In the present study, we investigated whether PLD2 is involved in axonal outgrowth using PC12 cells and primary cultured cerebellar granule neurons.(1)Phospholipase D2 Functions as a Downstream Signaling Molecule of MAP kinase Pathway in L1-Stimulated Neurite Outgrowth of Cerebellar Granule:In the cerebellum of postnatal day 8 mice, PLD2 protein was abundantly expressed, while PLD1 was not detected. The L1-stimulated neurite outgrowth was inhibited by overexpression of lipase-deficient (LD) PLD2. Furthermore, it was found that L1 stimulation in CGNs increased PLD activity concomitantly with phosphorylation of extracellular signal-regulated kinase (ERK … More ), both of which were inhibited by the MAP kinase-ERK kinase (MEK) inhibitor. These results provide evidence that PLD2 functions as a downstream signaling molecule of ERK to mediate the L1-dependent neurite outgrowth of CGNs, a mechanism that may be related to alcohol-related neurodevelopmental disorders.(2)Essential Role of Phospholipase D2 Activation Downstream of ERK MAP Kinase in the Signaling Pathway of NGF-Stimulated Neurite Outgrowth in PC12 Cells:Increased expression of wild type PLD2 (WT-PLD2), but not WT-PLD1,in a PC12 clonal cell line dramatically elongated neurites induced by NGF stimulation or transient expression of the active form of MAP kinase-ERK kinase (MEK-CA). In contrast, neurite elongation was inhibited by expression of LD-PLD2. Furthermore, the MEK inhibitor suppressed PLD2 activation and the hypertrophic neurite extension induced by NGF in PC12 cells inducibly expressing WT-PLD2. MEK-CA stimulated the activity of co-expressed PLD2. These results provide evidence that PLD2 functions as a downstream signaling molecule of ERK in the signaling pathway of the NGF-induced neurite outgrowth of PC 12 cells. Less

哺乳动物磷脂酶D（PLD）是一种新型信号转导酶，据信它在多种细胞功能中起着作用。已经鉴定出两个哺乳动物PLD同工酶PLD1和PLD2。尽管PLD1的激活机制和物理功能已经有充分的文献记录，但PLD2的激活机制和物理功能仍然有待储存。在本研究中，我们研究了PLD2是否使用PC12细胞和原发性培养的脑颗粒神经元参与轴突产生。（1）磷脂酶D2在L1刺激的神经素植物中的磷脂激酶途径的下游信号分子中起作用。绝对表示，而未检测到PLD1。 L1刺激的神经元生长受到脂肪酶缺陷（LD）PLD2的过表达抑制。此外，发现CGN中的L1模拟与细胞外信号调节激酶（ERK…更多）的磷酸化同时增加了PLD活性，这两种激酶均被MAP激酶-ERK激酶（MEK）抑制剂抑制。 These results provide evidence that PLD2 functions as a downstream signaling molecule of ERK to mediate the L1-dependent neuronal outgrowth of CGNs, a mechanism that (2)Essential Role of Phospholipase D2 Activation Downstream of ERK MAP Kinase in the Signaling Pathway of NGF-Stimulated Neurite Outgrowth in PC12 Cells:Increased expression of wild type PLD2 (WT-PLD2), but not WT-PLD1，在PC12克隆细胞系中，由NGF刺激或MAP激酶-ERK激酶（MEK-CA）的活性形式引起的神经发育疾病（MEK-CA）引起的急剧伸长的神经发育障碍。相反，LD-PLD2的表达抑制了神经牵引伸长。此外，MEK抑制剂抑制了pC12细胞中NGF诱导的PC12细胞诱导的PLD2激活和诱导表达WT-PLD2的肥厚神经蛋白延伸。 MEK-CA刺激了共表达PLD2的活性。这些结果提供了证据表明，PLD2在NGF诱导的PC 12细胞的神经蛋白神经蛋白产物的信号传导途径中充当ERK的下游信号分子。较少的