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

• DOI: 10.1016/j.neuron.2010.01.007
• Publication Date: 2010-02-11T11:53:40Z
• Authors: Hiroshi Kawabe; Antje Neeb; Kalina Dimova; Samuel M. Young; Michiko Takeda; Shutaro Katsuraba...; Miso Mitkovski; Oxana A. Malakhova; Dong-Er Zhang; Masato Umikawa; Ken-ichi Kariya; Sandra Goebbels; Klaus-Armin Nave; Christian Rosenmund; Olaf Jahn; JeongSeop Rhee; Nils Brose
• Keywords: NEDD4; Neurite; Ubiquitin-Protein Ligases

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.