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Wnt-5a increases NO and modulates NMDA receptor in rat hippocampal neurons |
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| Authors: | Francisco J Muñoz Juan A Godoy Waldo Cerpa Inés M Poblete Juan Pablo Huidobro-Toro Nibaldo C Inestrosa |
| Institution: | 1. 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;2. Laboratory of Molecular Physiology and Channelopathies, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Parc de Recerca Biomédica de Barcelona, Spain;3. 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;4. Departamento de Fisiología, Facultad de Ciencias Biológicas, P. Universidad Católica de Chile, Santiago de Chile, Chile;5. Departamento de Biología, Facultad de Química y Biología, Universidad de Santiago, Santiago de Chile, Chile;6. Centre for Healthy Brain Ageing, School of Psychiatry, UNSW, Faculty of Medicine, University of New South Wales, Sydney, Australia |
| Abstract: | 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. |
| Keywords: | Wnt-5a Wingless-type family member 5a NO nitric oxide NMDAR N-methyl-d-aspartate receptor sFRP-2 soluble Frizzled related protein-2 Wnt/PCP Wnt/planar cell polarity JNK c-Jun N-terminal kinase CaMKII Ca2+/calmodulin dependent kinase II PKC protein kinase C Calcineurin Protein phosphatase GABA γ-Aminobutiric acid nNOS neuronal NO synthase SNP sodium nitroprusside dehydrate 7-NI 7-nitroindazole BAPTA-AM 2-bis-(o-aminophenoxy)-ethane-N N N&prime N&prime tetraaceticacid tetraacetoxymethyl ester CRD cysteine rich domain AraC cytosine arabinoside DIV days in vitro GFAP glial fibrillary acidic protein BSA bovine serum albumin |
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