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

First Author  Cerpa W Year  2015
Journal  Proc Natl Acad Sci U S A Volume  112
Issue  15 Pages  4797-802
PubMed ID  25825749 Mgi Jnum  J:220532
Mgi Id  MGI:5635310 Doi  10.1073/pnas.1417053112
Citation  Cerpa W, et al. (2015) RoR2 functions as a noncanonical Wnt receptor that regulates NMDAR-mediated synaptic transmission. Proc Natl Acad Sci U S A 112(15):4797-802
abstractText  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.
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