title: Silencing or knocking out the Na(+)/Ca(2+) exchanger-3 (NCX3) impairs oligodendrocyte differentiation.
abstract: Changes in intracellular [Ca(2+)](i) levels have been shown to influence developmental processes that accompany the transition of human oligodendrocyte precursor cells (OPCs) into mature myelinating oligodendrocytes and are required for the initiation of the myelination and re-myelination processes. In the present study, we explored whether calcium signals mediated by the selective sodium calcium exchanger (NCX) family members NCX1, NCX2, and NCX3, play a role in oligodendrocyte maturation. Functional studies, as well as mRNA and protein expression analyses, revealed that NCX1 and NCX3, but not NCX2, were divergently modulated during OPC differentiation into oligodendrocyte phenotype. In fact, whereas NCX1 was downregulated, NCX3 was strongly upregulated during oligodendrocyte development. The importance of calcium signaling mediated by NCX3 during oligodendrocyte maturation was supported by several findings. Indeed, whereas knocking down the NCX3 isoform in OPCs prevented the upregulation of the myelin protein markers 2',3'-cyclic nucleotide-3'-phosphodiesterase (CNPase) and myelin basic protein (MBP), its overexpression induced an upregulation of CNPase and MBP. Furthermore, NCX3-knockout mice showed not only a reduced size of spinal cord but also marked hypo-myelination, as revealed by decrease in MBP expression and by an accompanying increase in OPC number. Collectively, our findings indicate that calcium signaling mediated by NCX3 has a crucial role in oligodendrocyte maturation and myelin formation.
authors.affiliation: Fondazione IRCSS SDN, Naples, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Boscia
authors.forename: C
authors.initials: C
authors.lastname: D'Avanzo
authors.forename: A
authors.initials: A
authors.lastname: Pannaccione
authors.forename: A
authors.initials: A
authors.lastname: Secondo
authors.forename: A
authors.initials: A
authors.lastname: Casamassa
authors.forename: L
authors.initials: L
authors.lastname: Formisano
authors.forename: N
authors.initials: N
authors.lastname: Guida
authors.forename: Sophie
authors.initials: S
authors.lastname: Sokolow
authors.forename: André
authors.initials: A
authors.lastname: Herchuelz
authors.forename: L
authors.initials: L
authors.lastname: Annunziato
mesh_terms: D000818:Animals; D020013:Calcium Signaling / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D005786:Gene Expression Regulation / Q000502:physiology; D020868:Gene Silencing; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D009186:Myelin Sheath / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D058953:Neural Stem Cells / Q000166:cytology / Q000378:metabolism*; D009836:Oligodendroglia / Q000166:cytology / Q000378:metabolism*; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D019831:Sodium-Calcium Exchanger / Q000096:biosynthesis* / Q000235:genetics
chemical_list: C499849:NCX1 protein, mouse; D009419:Nerve Tissue Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; C101832:SLC38A3 protein, human; C491739:Slc8a2 protein, mouse; C110927:Slc8a2 protein, rat; C491101:Slc8a3 protein, mouse; C491102:Slc8a3 protein, rat; D019831:Sodium-Calcium Exchanger; C110374:sodium-calcium exchanger 1