Regulation of Rap2A by the Ubiquitin Ligase Nedd4-1 Controls Neurite Development

被引：176

作者：

Kawabe, Hiroshi ^{[1
]}

Neeb, Antje ^{[1
]}

Dimova, Kalina ^{[1
,2
,3
]}

Young, Samuel M., Jr. ^{[4
]}

Takeda, Michiko ^{[1
]}

Katsurabayashi, Shutaro ^{[4
]}

Mitkovski, Miso ^{[5
]}

Malakhova, Oxana A. ^{[6
]}

Zhang, Dong-Er ^{[6
,7
,8
]}

Ulmilkawa, Masato ^{[9
]}

Kariya, Ken-ichi ^{[9
]}

Goebbels, Sandra ^{[10
]}

Nave, Klaus-Armin ^{[10
]}

Rosenmund, Christian ^{[4
]}

Jahn, Olaf ^{[2
,3
]}

Rhee, JeongSeop ^{[1
,4
]}

Brose, Nils ^{[1
]}

机构：

[1] Max Planck Inst Expt Med, Dept Mol Neurobiol, D-37075 Gottingen, Germany

[2] Max Planck Inst Expt Med, Prote Grp, D-37075 Gottingen, Germany

[3] DFG CMPB, D-37075 Gottingen, Germany

[4] Max Planck Inst Biophys Chem, Dept Membrane Biophys, D-37077 Gottingen, Germany

[5] Max Planck Inst Expt Med, Imaging Facil, D-37075 Gottingen, Germany

[6] Scripps Res Inst, Dept Mol & Expt Med, La Jolla, CA 92037 USA

[7] Univ Calif San Diego, Dept Pathol, La Jolla, CA 92093 USA

[8] Univ Calif San Diego, Div Biol, La Jolla, CA 92093 USA

[9] Univ Ryukyus, Div Cell Biol, Grad Sch Med, Nishihara, Okinawa 9030215, Japan

[10] Max Planck Inst Expt Med, Dept Neurogenet, D-37075 Gottingen, Germany

来源：

NEURON | 2010年 / 65卷 / 03期

基金：

美国国家卫生研究院; 日本学术振兴会;

关键词：

NUCLEOTIDE EXCHANGE FACTOR; SYNAPSE ELIMINATION; HIPPOCAMPAL-NEURONS; PUTATIVE EFFECTOR; PYRAMIDAL NEURONS; ANGELMAN SYNDROME; CORTICAL-NEURONS; PROTEIN-KINASE; WW DOMAINS; PHOSPHORYLATION;

D O I：

10.1016/j.neuron.2010.01.007

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

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.

引用

页码：358 / 372

页数：15

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