How CD40L reverse signaling regulates axon and dendrite growth.
How CD40L reverse signaling regulates axon and dendrite growth.
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DOI：
10.1007/s00018-020-03563-2
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发表时间：
2021-03
期刊：
影响因子：
--
通讯作者：
Davies AM
中科院分区：
文献类型：
--
作者：
Carriba P;Davies AM
CD 40激活的CD 40 L反向信号是发育中海马锥体神经元轴突和树突生长的主要生理调节剂。在这里，我们研究了CD 40 L介导的反向信号如何促进这些过程的生长。从Cd 40 −/−小鼠胚胎中建立海马锥体神经元的培养物，以消除内源性CD 40/CD 40 L信号传导，并通过CD 40-Fc嵌合体刺激CD 40 L反向信号传导。CD 40 L反向信号增加了PKC、ERK和JNK信号通路中蛋白的磷酸化并因此激活。这些途径的药理学激活剂和抑制剂显示，而JNK的激活抑制生长，PKC和ERK 1/ERK 2的激活增强生长。使用药理学试剂组合的实验表明，这些信号通路通过作为相互关联和相互依赖的网络而不是以简单的线性序列起作用来调节生长。免疫沉淀研究表明，刺激CD 40 L反向信号产生了一个受体复合物，包括CD 40 L，PKCβ和Syk酪氨酸激酶。我们的研究已经开始阐明分子网络和相互作用，促进轴突和树突生长发育的海马神经元后，激活CD 40 L反向信号。本文的在线版本（10.1007/s 00018 -020-03563-2）包含补充材料，可供授权用户使用。
CD40-activated CD40L reverse signaling is a major physiological regulator of axon and dendrite growth from developing hippocampal pyramidal neurons. Here we have studied how CD40L-mediated reverse signaling promotes the growth of these processes. Cultures of hippocampal pyramidal neurons were established from Cd40−/− mouse embryos to eliminate endogenous CD40/CD40L signaling, and CD40L reverse signaling was stimulated by a CD40-Fc chimera. CD40L reverse signaling increased phosphorylation and hence activation of proteins in the PKC, ERK, and JNK signaling pathways. Pharmacological activators and inhibitors of these pathways revealed that whereas activation of JNK inhibited growth, activation of PKC and ERK1/ERK2 enhanced growth. Experiments using combinations of pharmacological reagents revealed that these signaling pathways regulate growth by functioning as an interconnected and interdependent network rather than acting in a simple linear sequence. Immunoprecipitation studies suggested that stimulation of CD40L reverse signaling generated a receptor complex comprising CD40L, PKCβ, and the Syk tyrosine kinase. Our studies have begun to elucidate the molecular network and interactions that promote axon and dendrite growth from developing hippocampal neurons following activation of CD40L reverse signaling. The online version of this article (10.1007/s00018-020-03563-2) contains supplementary material, which is available to authorized users.
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DOI：
10.1073/pnas.251194298
发表时间：
2001-11-20
影响因子：
11.1
作者：
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