泛素连接酶 Nedd4-1 对 Rap2A 的调控控制着神经突的发育。
Regulation of Rap2A by the ubiquitin ligase Nedd4-1 controls neurite development.
机构信息
Department of Molecular Neurobiology, Max Planck Institute of Experimental Medicine, 37075 Göttingen, Germany.
出版信息
Neuron. 2010 Feb 11;65(3):358-72. doi: 10.1016/j.neuron.2010.01.007.
Abstract
Nedd4-1 is a "neuronal precursor cell expressed and developmentally downregulated protein" and among the most abundant E3 ubiquitin ligases in mammalian neurons. In analyses of conventional and conditional Nedd4-1-deficient mice, we found that Nedd4-1 plays a critical role in dendrite formation. Nedd4-1, the serine/threonine kinase TNIK, and Rap2A form a complex that controls Nedd4-1-mediated ubiquitination of Rap2A. Ubiquitination by Nedd4-1 inhibits Rap2A function, which reduces the activity of Rap2 effector kinases of the TNIK family and promotes dendrite growth. We conclude that a Nedd4-1/Rap2A/TNIK signaling pathway regulates neurite growth and arborization in mammalian neurons.
摘要
Nedd4-1 是一种“神经前体细胞表达和发育下调蛋白”，也是哺乳动物神经元中最丰富的 E3 泛素连接酶之一。在对传统和条件性 Nedd4-1 缺失小鼠的分析中，我们发现 Nedd4-1 在树突形成中发挥着关键作用。Nedd4-1、丝氨酸/苏氨酸激酶 TNIK 和 Rap2A 形成一个复合物，控制 Nedd4-1 介导的 Rap2A 的泛素化。Nedd4-1 的泛素化抑制 Rap2A 的功能，从而降低了 TNIK 家族的 Rap2 效应激酶的活性，并促进树突生长。我们得出结论，Nedd4-1/Rap2A/TNIK 信号通路调节哺乳动物神经元中的神经突生长和分支。
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