Authors:
Hiroshi Kawabe, Antje Neeb, Kalina Dimova, Samuel M. Young, Michiko Takeda, Shutaro Katsurabayashi, 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
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.
Source:
Neuron; Vol. 65, Issue 3, 358-372 (02/11/10)