title: SVCT2 Overexpression in Neuroblastoma Cells Induces Cellular Branching that is Associated with ERK Signaling.
abstract: Expression of the sodium and ascorbic acid (AA) cotransporter SVCT2 is induced during the period of cellular arborization and synaptic maturation of early postnatal (P1-P5) rat cerebral neurons. The physiological importance of the transporter for neurons is evidenced by the lethality and delayed neuronal differentiation detected in mice with ablation of SVCT2. The mechanism(s) involved in these defects and the role of SVCT2 in neuronal branching have not been determined yet. To address this, we used lentiviral expression vectors to increase the levels of SVCT2 in N2a cells and analyzed the effects on neurite formation. Expression of a fusion protein containing the human SVCT2wt and EYFP induced an increase in the number of MAP2+ neurites and filopodia in N2a cells. Overexpression of SVCT2 and treatment with AA promoted ERK1/2 phosphorylation. Our data suggest that enhanced expression of the high affinity AA transporter SVCT2, which tightly regulates intracellular AA concentrations, induces neuronal branching that then activates key signaling pathways that are involved in the differentiation and maturation of cortical neurons during postnatal development.
authors.affiliation: Laboratory of Neurobiology and Stem Cells, Center for Advanced Microscopy CMA BIO BIO, Faculty of Biological Sciences, University of Concepcion, Concepción, Chile.
authors.forename: Katterine
authors.initials: K
authors.lastname: Salazar
authors.affiliation: Laboratory of Neurobiology and Stem Cells, Center for Advanced Microscopy CMA BIO BIO, Faculty of Biological Sciences, University of Concepcion, Concepción, Chile.
authors.forename: Milka
authors.initials: M
authors.lastname: Martínez
authors.affiliation: Laboratory of Neurobiology and Stem Cells, Center for Advanced Microscopy CMA BIO BIO, Faculty of Biological Sciences, University of Concepcion, Concepción, Chile.
authors.forename: Viviana
authors.initials: V
authors.lastname: Ulloa
authors.affiliation: Laboratory of Neurobiology and Stem Cells, Center for Advanced Microscopy CMA BIO BIO, Faculty of Biological Sciences, University of Concepcion, Concepción, Chile.
authors.forename: Romina
authors.initials: R
authors.lastname: Bertinat
authors.affiliation: Laboratory of Neurobiology and Stem Cells, Center for Advanced Microscopy CMA BIO BIO, Faculty of Biological Sciences, University of Concepcion, Concepción, Chile.
authors.forename: Fernando
authors.initials: F
authors.lastname: Martínez
authors.affiliation: Laboratory of Neurobiology and Stem Cells, Center for Advanced Microscopy CMA BIO BIO, Faculty of Biological Sciences, University of Concepcion, Concepción, Chile.
authors.forename: Nery
authors.initials: N
authors.lastname: Jara
authors.affiliation: Laboratory of Neurobiology and Stem Cells, Center for Advanced Microscopy CMA BIO BIO, Faculty of Biological Sciences, University of Concepcion, Concepción, Chile.
authors.forename: Francisca
authors.initials: F
authors.lastname: Espinoza
authors.affiliation: Department of Anatomy and Cell Biology, College of Medicine, University of Illinois Chicago, Chicago, IL, USA.
authors.forename: Ernesto R
authors.initials: ER
authors.lastname: Bongarzone
authors.affiliation: Laboratory of Neurobiology and Stem Cells, Center for Advanced Microscopy CMA BIO BIO, Faculty of Biological Sciences, University of Concepcion, Concepción, Chile. frnualart@udec.cl.
authors.forename: Francisco
authors.initials: F
authors.lastname: Nualart
mesh_terms: D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D048430:Cell Shape; D019587:Dietary Supplements; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D020935:MAP Kinase Signaling System; D051379:Mice; D009447:Neuroblastoma / Q000378:metabolism* / Q000473:pathology*; D010641:Phenotype; D010766:Phosphorylation / Q000187:drug effects; D021381:Protein Transport; D060347:Sodium-Coupled Vitamin C Transporters / Q000378:metabolism*
chemical_list: C555163:SLC23A2 protein, human; D060347:Sodium-Coupled Vitamin C Transporters; D048049:Extracellular Signal-Regulated MAP Kinases; D001205:Ascorbic Acid
keywords: Branching; Filopodia; N2a cells; SVCT1; SVCT2; Vitamin C