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Neuron. 2010 Feb 11;65(3):358-72. doi: 10.1016/j.neuron.2010.01.007.

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

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1
Department of Molecular Neurobiology, Max Planck Institute of Experimental Medicine, 37075 Göttingen, Germany. kawabe@em.mp.de

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.

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PMID:
20159449
PMCID:
PMC2825371
DOI:
10.1016/j.neuron.2010.01.007
[Indexed for MEDLINE]
Free PMC Article

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