The catalytic activity, but not receptor binding, of sPLA2s plays a critical role for neurite outgrowth induction in PC12 cells

The catalytic activity, but not receptor binding, of sPLA2s plays a critical role for neurite outgrowth induction in PC12 cells
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DOI:
10.1016/j.brainres.2004.04.069
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发表时间:
2004-07-23
期刊:
影响因子:
2.9
通讯作者:
Arioka, M
Arioka, M
中科院分区:
医学3区
文献类型:
--
作者:
Nakashima, S;Kitamoto, K;Arioka, M

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我们先前发现真菌分泌型磷脂酶A(2)(sPLA(2))以L型钙通道活性依赖的方式诱导PC 12细胞中神经突的形成。在这项研究中,我们比较了不同sPLA(2)的神经突诱导活性,包括蜂毒sPLA(2)(bvPLA(2)),并发现它与每个sPLA 2从活的PC 12细胞释放脂肪酸的能力相关。一致地,使用bvPLA2的几个突变体,我们发现酶活性而不是与神经毒性sPLA(2)s的假定N型受体的结合活性是神经突发生反应的关键决定因素。这些结果表明,神经突起的生长是由膜磷脂降解后产生的信使引起的。(C)2004 Elsevier B.V.保留所有权利。
We previously showed that fungal secretory phospholipase A(2) (sPLA(2)) induces neurite formation in PC 12 cells in an L-type Ca2+ channel activity-dependent manner. In this study we compared neurite-inducing activity of different sPLA(2)s, including bee venom sPLA(2) (bvPLA(2)), and found that it correlated with the ability of each sPLA2 to release fatty acids from live PC12 cells. Consistently, using several mutants of bvPLA2, we found that the enzymatic activity rather than the binding activity to the putative N-type receptor for neurotoxic sPLA(2)s is the critical determinant for the neuritogenic response. These results imply that the neurite outgrowth is elicited by the messenger(s) produced upon degradation of membrane phospholipids. (C) 2004 Elsevier B.V. All rights reserved.