RoR2 functions as a noncanonical Wnt receptor that regulates NMDAR-mediated synaptic transmission

被引：33

作者：

Cerpa, Waldo ^{[1
]}

Latorre-Esteves, Elena ^{[1
,2
]}

Barria, Andres ^{[1
]}

机构：

[1] Univ Washington, Dept Physiol & Biophys, Seattle, WA 98195 USA

[2] Univ Washington, Mol & Cellular Biol Program, Seattle, WA 98195 USA

来源：

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2015年 / 112卷 / 15期

基金：

美国国家卫生研究院;

关键词：

NMDA receptors; Wnt signaling; synaptic transmission; RoR2; glutamate receptors; PROTEIN-KINASE-C; SIGNALING PATHWAY; TYROSINE KINASES; ALZHEIMERS-DISEASE; NERVOUS-SYSTEM; TRAFFICKING; PLASTICITY; SCHIZOPHRENIA; PHOSPHORYLATION; ACTIVATION;

D O I：

10.1073/pnas.1417053112

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Wnt signaling has a well-established role as a regulator of nervous system development, but its role in the maintenance and regulation of established synapses in the mature brain remains poorly understood. At excitatory glutamatergic synapses, NMDA receptors (NMDARs) have a fundamental role in synaptogenesis, synaptic plasticity, and learning and memory; however, it is not known what controls their number and subunit composition. Here we show that the receptor tyrosine kinase-like orphan receptor 2 (RoR2) functions as a Wnt receptor required to maintain basal NMDAR-mediated synaptic transmission. In addition, RoR2 activation by a noncanonical Wnt ligand activates PKC and JNK and acutely enhances NMDAR synaptic responses. Regulation of a key component of glutamatergic synapses through RoR2 provides a mechanism for Wnt signaling to modulate synaptic transmission, synaptic plasticity, and brain function acutely beyond embryonic development.

引用

页码：4797 / 4802

页数：6

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