Portal de Periódicos da CAPES

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

2010; Cell Press; Volume: 65; Issue: 3 Linguagem: Inglês

10.1016/j.neuron.2010.01.007

1097-4199

Hiroshi Kawabe, Antje Neeb, Kalina Dimova, Samuel Young, Michiko Takeda, Shutaro Katsurabayashi, Mišo Mitkovski, Oxana A. Malakhova, Dong‐Er Zhang, Masato Umikawa, Ken‐ichi Kariya, Sandra Goebbels, Klaus‐Armin Nave, Christian Rosenmund, Olaf Jahn, Jeong-Seop Rhee, Nils Brose,

Protein Degradation and Inhibitors

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.