Regulation of Rap2A by the Ubiquitin Ligase Nedd4-1 Controls Neurite Development
Copyright policy )Regulation of Rap2A by the Ubiquitin Ligase Nedd4-1 Controls Neurite Development
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.
- Max Planck Society Germany
- University of California, San Diego United States
- University of the Ryukyus Japan
- University of Göttingen Germany
- Scripps Research Institute United States
Patch-Clamp Techniques, Neuroscience(all), Nedd4 Ubiquitin Protein Ligases, Green Fluorescent Proteins, Hippocampus, MOLNEURO, Germinal Center Kinases, Membrane Potentials, Mice, Neurites, Animals, Humans, Myelin Proteolipid Protein, Cells, Cultured, Mice, Knockout, Neurons, Endosomal Sorting Complexes Required for Transport, Gene Expression Regulation, Developmental, Coculture Techniques, Animals, Newborn, SIGNALING, CELLBIO, Microglia, Protein Binding
Patch-Clamp Techniques, Neuroscience(all), Nedd4 Ubiquitin Protein Ligases, Green Fluorescent Proteins, Hippocampus, MOLNEURO, Germinal Center Kinases, Membrane Potentials, Mice, Neurites, Animals, Humans, Myelin Proteolipid Protein, Cells, Cultured, Mice, Knockout, Neurons, Endosomal Sorting Complexes Required for Transport, Gene Expression Regulation, Developmental, Coculture Techniques, Animals, Newborn, SIGNALING, CELLBIO, Microglia, Protein Binding
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