Wnt-5a increases NO and modulates NMDA receptor in rat hippocampal neurons.
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/Ca(2+) signaling through a mechanism that depends on Ca(2+) 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.
Centro de Envejecimiento y Regeneración (CARE), Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, P. Universidad Católica de Chile, Santiago de Chile, Chile; Laboratory of Molecular Physiology and Channelopathies, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Parc de Recerca Biomédica de Barcelona, Spain.
Francisco J
FJ
Muñoz
Centro de Envejecimiento y Regeneración (CARE), Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, P. Universidad Católica de Chile, Santiago de Chile, Chile.
Juan A
JA
Godoy
Laboratorio de Función y Patología Neuronal, Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, P. Universidad Católica de Chile, Santiago de Chile, Chile.
Waldo
W
Cerpa
Centro de Envejecimiento y Regeneración (CARE), Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, P. Universidad Católica de Chile, Santiago de Chile, Chile; Departamento de Fisiología, Facultad de Ciencias Biológicas, P. Universidad Católica de Chile, Santiago de Chile, Chile.
Inés M
IM
Poblete
Centro de Envejecimiento y Regeneración (CARE), Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, P. Universidad Católica de Chile, Santiago de Chile, Chile; Departamento de Fisiología, Facultad de Ciencias Biológicas, P. Universidad Católica de Chile, Santiago de Chile, Chile; Departamento de Biología, Facultad de Química y Biología, Universidad de Santiago, Santiago de Chile, Chile.
Juan Pablo
JP
Huidobro-Toro
Centro de Envejecimiento y Regeneración (CARE), Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, P. Universidad Católica de Chile, Santiago de Chile, Chile; Centre for Healthy Brain Ageing, School of Psychiatry, UNSW, Faculty of Medicine, University of New South Wales, Sydney, Australia. Electronic address: ninestrosa@bio.puc.cl.
Nibaldo C
NC
Inestrosa
D000818:Animals; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D057809:HEK293 Cells; D006624:Hippocampus / Q000166:cytology / Q000196:embryology; D006801:Humans; D007739:L Cells; D008565:Membrane Proteins / Q000494:pharmacology; D051379:Mice; D008954:Models, Biological; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D051153:Wnt Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000494:pharmacology; D000071818:Wnt-5a Protein; D000094742:Secreted Frizzled-Related Proteins
D002118:Calcium; D008565:Membrane Proteins; D009569:Nitric Oxide; D016194:Receptors, N-Methyl-D-Aspartate; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; C121001:NR2B NMDA receptor; C503650:Sfrp2 protein, rat; D000094742:Secreted Frizzled-Related Proteins; C491837:Wnt5a protein, rat
2-bis-(o-aminophenoxy)-ethane-N,N,N′,N′tetraaceticacid,tetraacetoxymethyl ester; 7-NI; 7-nitroindazole; AraC; BAPTA-AM; BSA; CRD; Ca(2+)/calmodulin dependent kinase II; CaMKII; Calcineurin; DIV; GABA; GFAP; GluN2B subunit; JNK; N-methyl-d-aspartate receptor; NMDAR; NO; PKC; Protein phosphatase; Ryanodine receptors; SNP; Wingless-type family member 5a; Wnt-5a; Wnt/PCP; Wnt/planar cell polarity; bovine serum albumin; c-Jun N-terminal kinase; cysteine rich domain; cytosine arabinoside; days in vitro; glial fibrillary acidic protein; nNOS; neuronal NO synthase; nitric oxide; protein kinase C; sFRP-2; sodium nitroprusside dehydrate; soluble Frizzled related protein-2; γ-Aminobutiric acid