Journal article
Regulation of Rap2A by the Ubiquitin Ligase Nedd4-1 Controls Neurite Development
Neuron (Cambridge, Mass.), Vol.65(3), pp.358-372
2010
DOI: 10.1016/j.neuron.2010.01.007
PMCID: PMC2825371
PMID: 20159449
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.
► The E3 ubiquitin ligase Nedd4-1 mono-/diubiquitinates the small GTPase Rap2 ► Ubiquitinated Rap2 cannot activate the kinase TNIK, a dendrite growth regulator ► Nedd4-1/Rap2/TNIK signaling in neurons was perturbed by genetic methods ► Perturbation of Nedd4-1/Rap2/TNIK signaling reduces neuronal dendrite growth
Details
- Title: Subtitle
- Regulation of Rap2A by the Ubiquitin Ligase Nedd4-1 Controls Neurite Development
- Creators
- Hiroshi Kawabe - Department of Molecular Neurobiology, Max Planck Institute of Experimental Medicine, 37075 Göttingen, GermanyAntje Neeb - Department of Molecular Neurobiology, Max Planck Institute of Experimental Medicine, 37075 Göttingen, GermanyKalina Dimova - Department of Molecular Neurobiology, Max Planck Institute of Experimental Medicine, 37075 Göttingen, GermanySamuel M Young - Department of Membrane Biophysics, Max Planck Institute of Biophysical Chemistry, 37077 Göttingen, GermanyMichiko Takeda - Department of Molecular Neurobiology, Max Planck Institute of Experimental Medicine, 37075 Göttingen, GermanyShutaro Katsurabayashi - Department of Membrane Biophysics, Max Planck Institute of Biophysical Chemistry, 37077 Göttingen, GermanyMiso Mitkovski - Imaging Facility, Max Planck Institute of Experimental Medicine, 37075 Göttingen, GermanyOxana A Malakhova - Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USADong-Er Zhang - Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USAMasato Umikawa - Division of Cell Biology, Graduate School of Medicine, University of the Ryukyus, Nishihara-cho, Okinawa 903-0215, JapanKen-ichi Kariya - Division of Cell Biology, Graduate School of Medicine, University of the Ryukyus, Nishihara-cho, Okinawa 903-0215, JapanSandra Goebbels - Department of Neurogenetics, Max Planck Institute of Experimental Medicine, 37075 Göttingen, GermanyKlaus-Armin Nave - Department of Neurogenetics, Max Planck Institute of Experimental Medicine, 37075 Göttingen, GermanyChristian Rosenmund - Department of Membrane Biophysics, Max Planck Institute of Biophysical Chemistry, 37077 Göttingen, GermanyOlaf Jahn - Proteomics Group, Max Planck Institute of Experimental Medicine and DFG-CMPB, 37075 Göttingen, GermanyJeongSeop Rhee - Department of Molecular Neurobiology, Max Planck Institute of Experimental Medicine, 37075 Göttingen, GermanyNils Brose - Department of Molecular Neurobiology, Max Planck Institute of Experimental Medicine, 37075 Göttingen, Germany
- Resource Type
- Journal article
- Publication Details
- Neuron (Cambridge, Mass.), Vol.65(3), pp.358-372
- Publisher
- Elsevier Inc
- DOI
- 10.1016/j.neuron.2010.01.007
- PMID
- 20159449
- PMCID
- PMC2825371
- ISSN
- 0896-6273
- eISSN
- 1097-4199
- Language
- English
- Date published
- 2010
- Academic Unit
- Anatomy and Cell Biology; Iowa Neuroscience Institute; Otolaryngology
- Record Identifier
- 9984025345802771
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