RGD Reference Report - Regulation of Rap2A by the ubiquitin ligase Nedd4-1 controls neurite development. - Rat Genome Database

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

Authors: Kawabe, H  Neeb, A  Dimova, K  Young SM, JR  Takeda, M  Katsurabayashi, S  Mitkovski, M  Malakhova, OA  Zhang, DE  Umikawa, M  Kariya, K  Goebbels, S  Nave, KA  Rosenmund, C  Jahn, O  Rhee, J  Brose, N 
Citation: Kawabe H, etal., Neuron. 2010 Feb 11;65(3):358-72. doi: 10.1016/j.neuron.2010.01.007.
RGD ID: 8554407
Pubmed: PMID:20159449   (View Abstract at PubMed)
PMCID: PMC2825371   (View Article at PubMed Central)
DOI: DOI:10.1016/j.neuron.2010.01.007   (Journal Full-text)

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.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
protein K63-linked ubiquitination involved_inIDA 8554407PMID:20159449UniProt 
regulation of dendrite morphogenesis involved_inIDA 8554407PMID:20159449UniProt 

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
synapse is_active_inIDA 8554407PMID:20159449SynGO 
synapse is_active_inIEP 8554407PMID:20159449SynGO 
synaptic membrane is_active_inIDA 8554407PMID:20159449SynGO 
synaptic membrane is_active_inIEP 8554407PMID:20159449SynGO 

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
ubiquitin-protein transferase activity enablesIDA 8554407PMID:20159449UniProt 

Objects Annotated

Genes (Rattus norvegicus)
Nedd4  (NEDD4 E3 ubiquitin protein ligase)
Rap2a  (RAP2A, member of RAS oncogene family)


Additional Information