Wnt-5a increases NO and modulates NMDA receptor in rat hippocampal neurons

• Published in: Biochemical and biophysical research communications 2014-02, Vol.444 (2), p.189-194
• Main Authors: Muñoz, Francisco J., Godoy, Juan A., Cerpa, Waldo, Poblete, Inés M., Huidobro-Toro, Juan Pablo, Inestrosa, Nibaldo C.
• Format: Article
• Language: English
• Subjects: 2-bis-(o-aminophenoxy)-ethane-N,N,N′,N′tetraaceticacid,tetraacetoxymethyl ester; 7-NI; 7-nitroindazole; Animals; AraC; BAPTA-AM; Blotting, Western; bovine serum albumin; BSA; c-Jun N-terminal kinase; Ca2+/calmodulin dependent kinase II; Calcineurin; Calcium - metabolism; CaMKII; Cell Membrane - metabolism; Cells, Cultured; CRD; cysteine rich domain; cytosine arabinoside; days in vitro; DIV; GABA; GFAP; glial fibrillary acidic protein; GluN2B subunit; HEK293 Cells; Hippocampus - cytology; Hippocampus - embryology; Humans; JNK; L Cells (Cell Line); Membrane Proteins - pharmacology; Mice; Models, Biological; N-methyl-d-aspartate receptor; neuronal NO synthase; Neurons - cytology; Neurons - drug effects; Neurons - metabolism; nitric oxide; Nitric Oxide - metabolism; NMDAR; nNOS; PKC; protein kinase C; Protein phosphatase; Protein Transport - drug effects; Rats; Rats, Sprague-Dawley; Receptors, N-Methyl-D-Aspartate - metabolism; Ryanodine receptors; sFRP-2; Signal Transduction - drug effects; SNP; sodium nitroprusside dehydrate; soluble Frizzled related protein-2; Wingless-type family member 5a; Wnt Proteins - antagonists & inhibitors; Wnt Proteins - metabolism; Wnt Proteins - pharmacology; Wnt-5a; Wnt-5a Protein; Wnt/PCP; Wnt/planar cell polarity; γ-Aminobutiric acid
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2014.01.031

•Wnt-5a activates non-canonical Wnt/Ca2+ signaling increasing NO production.•This effect is depending on calcineurin activation from sarcoplasmic calcium.•NO evoked by Wnt-5a promotes GluN2B expression in neuronal membrane.•This signaling would be relevant for glutamatergic hippocampal function. Wnt signaling has a crucial role in synaptic function at the central nervous system. Here we evaluate whether Wnts affect nitric oxide (NO) generation in hippocampal neurons. We found that non-canonical Wnt-5a triggers NO production; however, Wnt-3a a canonical ligand did not exert the same effect. Co-administration of Wnt-5a with the soluble Frizzled related protein-2 (sFRP-2) a Wnt antagonist blocked the NO production. Wnt-5a activates the non-canonical Wnt/Ca2+ signaling through a mechanism that depends on Ca2+ release from Ryanodine-sensitive internal stores. The increase in NO levels evoked by Wnt-5a promotes the insertion of the GluN2B subunit of the NMDA receptor (NMDAR) into the neuronal cell surface. To the best of our knowledge, this is the first time that Wnt-5a signaling is related to NO production, which in turn increases NMDARs trafficking to the cell surface.