A Wnt/Calcium Signaling Cascade Regulates Neuronal Excitability and Trafficking of NMDARs

• Main Authors: Andrea McQuate, Elena Latorre-Esteves, Andres Barria
• Format: Article
• Language: English
• Published: Elsevier 2017-10-01
• Series: Cell Reports
• Subjects: Wnt signaling; Wnt/Ca2+ signaling cascade; NMDARs; neuronal excitability; glutamatergic synaptic transmission; N-methyl-D-aspartate receptor
• Online Access: http://www.sciencedirect.com/science/article/pii/S2211124717312986

Wnt signaling controls multiple biological process, particularly the embryonic development of metazoans. Sustained expression of Wnt signaling components in the mature mammalian CNS and their apparent deregulation in certain neuropathologies suggest that it also plays a part beyond embryonic development to regulate normal brain function. We describe a noncanonical Wnt/Ca2+ signaling cascade that regulates the electrophysiological intrinsic properties of rat neurons, resulting in sustained membrane depolarization and the mobilization of Ca2+ from internal stores. These effects require tyrosine kinase-like orphan receptor 2 (RoR2), activation of PLC, and voltage-gated Ca2+ channels. Activation of this signaling cascade then promotes surface expression of N-methyl-D-aspartate receptors (NMDARs) through a SNARE-dependent mechanism. This neuronal Wnt/Ca2+ signaling pathway represents a mechanism for Wnt ligands to regulate normal brain processes in the mature animal and provides a framework for understanding how alterations in this pathway may contribute to the etiology of psychiatric disorders where NMDARs are compromised.