Regulation of Rap2A by the Ubiquitin Ligase Nedd4-1 Controls Neurite Development

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• 作者：Hiroshi Kawabe ; Antje Neeb ; Kalina Dimova ; Samuel M. Young Jr. ; Michiko Takeda ; Shutaro Katsurabayashi ; Miso Mitkovski ; Oxana A. Malakhova ; Dong-Er Zhang ; Masato Umikawa ; Ken-ichi Kariya ; S ; ra Goebbel
• 刊名：Neuron
• 出版年：2010
• 出版时间：11 February 2010
• 年：2010
• 卷：65
• 期：3
• 页码：358-372
• 全文大小：1925 K

文摘

Summary

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.