Journal
NEURON
Volume 65, Issue 3, Pages 358-372Publisher
CELL PRESS
DOI: 10.1016/j.neuron.2010.01.007
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Funding
- Deutsche Forschungsgemeinschaft [SFB271/B11]
- Japan Society for the Promotion of Science Postdoctoral Fellowship for Research Abroad
- Yamanouchi Foundation for Research on Metabolic Disorders
- Mochida Memorial Foundation for Medical and Pharmaceutical Research
- Alexander von Humboldt Foundation
- National Institutes of Health [NIH R01GM66955]
- Max Planck Society
- European Commission [LSHM-CT-2005-019055]
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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.
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