Regulation of Rap2A by the ubiquitin ligase Nedd4-1 controls neurite development

  • Neuron. 2010 Feb 11;65(3):358-72. doi: 10.1016/j.neuron.2010.01.007.
Hiroshi Kawabe  1 ,  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 ,  Sandra Goebbels ,  Klaus-Armin Nave ,  Christian Rosenmund ,  Olaf Jahn ,  JeongSeop Rhee ,  Nils Brose
Affiliations
  • 1. Department of Molecular Neurobiology, Max Planck Institute of Experimental Medicine, 37075 Göttingen, Germany. [email protected]
PMID: 20159449 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.