title: Wnt-5a ligand modulates mitochondrial fission-fusion in rat hippocampal neurons.
abstract: The Wnt signaling pathway plays an important role in developmental processes, including embryonic patterning, cell specification, and cell polarity. Wnt components participate in the development of the central nervous system, and growing evidence indicates that this pathway also regulates the function of the adult nervous system. In this study, we report that Wnt-5a, a noncanonical Wnt ligand, is a potent activator of mitochondrial dynamics and induces acute fission and fusion events in the mitochondria of rat hippocampal neurons. The effect of Wnt-5a was inhibited in the presence of sFRP, a Wnt scavenger. Similarly, the canonical Wnt-3a ligand had no effect on mitochondrial fission-fusion events, suggesting that this effect is specific for Wnt-5a alone. We also show that the Wnt-5a effects on mitochondrial dynamics occur with an increase in both intracellular and mitochondrial calcium (Ca(2+)), which was correlated with an increased phosphorylation of Drp1(Ser-616) and a decrease of Ser-637 phosphorylation, both indicators of mitochondrial dynamics. Electron microscope analysis of hippocampal tissues in the CA1 region showed an increase in the number of mitochondria present in the postsynaptic region, and this finding correlated with a change in mitochondrial morphology. We conclude that Wnt-5a/Ca(2+) signaling regulates the mitochondrial fission-fusion process in hippocampal neurons, a feature that might help to further understand the role of Wnt-related pathologies, including neurodegenerative diseases associated with mitochondrial dysfunction, and represents a potentially important link between impaired metabolic function and degenerative disorders.
authors.affiliation: From the Centro de Envejecimiento y Regeneración, Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, 8331150 Santiago, Chile.
authors.forename: Juan A
authors.initials: JA
authors.lastname: Godoy
authors.affiliation: From the Centro de Envejecimiento y Regeneración, Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, 8331150 Santiago, Chile.
authors.forename: Macarena S
authors.initials: MS
authors.lastname: Arrázola
authors.affiliation: From the Centro de Envejecimiento y Regeneración, Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, 8331150 Santiago, Chile.
authors.forename: Daniela
authors.initials: D
authors.lastname: Ordenes
authors.affiliation: From the Centro de Envejecimiento y Regeneración, Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, 8331150 Santiago, Chile.
authors.forename: Carmen
authors.initials: C
authors.lastname: Silva-Alvarez
authors.affiliation: the Centre for Healthy Brain Ageing, School of Psychiatry, Faculty of Medicine, University of New South Wales, Sydney, 2031 New South Wales, Australia, and.
authors.forename: Nady
authors.initials: N
authors.lastname: Braidy
authors.affiliation: From the Centro de Envejecimiento y Regeneración, Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, 8331150 Santiago, Chile, the Centre for Healthy Brain Ageing, School of Psychiatry, Faculty of Medicine, University of New South Wales, Sydney, 2031 New South Wales, Australia, and the Centro de Excelencia en Biomedicina de Magallanes, Universidad de Magallanes, 6200000 Punta Arenas, Chile ninestrosa@bio.puc.cl.
authors.forename: Nibaldo C
authors.initials: NC
authors.lastname: Inestrosa
mesh_terms: D000818:Animals; D056547:CA1 Region, Hippocampal / Q000166:cytology; D020013:Calcium Signaling; D002478:Cells, Cultured; D034281:Dynamins / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000502:physiology / Q000648:ultrastructure; D063154:Mitochondrial Dynamics; D009474:Neurons / Q000378:metabolism / Q000648:ultrastructure; D011499:Protein Processing, Post-Translational; D021381:Protein Transport; D017207:Rats, Sprague-Dawley; D051153:Wnt Proteins / Q000502:physiology*; D000071818:Wnt-5a Protein
chemical_list: D051153:Wnt Proteins; D000071818:Wnt-5a Protein; C491837:Wnt5a protein, rat; C486391:Dnm1l protein, mouse; D034281:Dynamins
keywords: Calcium; Mitochondria; Neurobiology; Signal Transduction; Wnt Signaling