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

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.

SUBMITTER: Kawabe H

PROVIDER: S-EPMC2825371 | biostudies-literature | 2010 Feb

REPOSITORIES: biostudies-literature

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

Kawabe Hiroshi H Neeb Antje A Dimova Kalina K Young Samuel M SM Takeda Michiko M Katsurabayashi Shutaro S Mitkovski Miso M Malakhova Oxana A OA Zhang Dong-Er DE Umikawa Masato M Kariya Ken-ichi K Goebbels Sandra S Nave Klaus-Armin KA Rosenmund Christian C Jahn Olaf O Rhee JeongSeop J Brose Nils N

Neuron 20100201 3

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 o ...[more]

PMID: 20159449

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