title: Nucleus-localized 21.5-kDa myelin basic protein promotes oligodendrocyte proliferation and enhances neurite outgrowth in coculture, unlike the plasma membrane-associated 18.5-kDa isoform.
abstract: The classic myelin basic protein (MBP) family of central nervous system (CNS) myelin arises from transcription start site 3 of the Golli (gene of oligodendrocyte lineage) complex and comprises splice isoforms ranging in nominal molecular mass from 14 kDa to (full-length) 21.5 kDa. We have determined here a number of distinct functional differences between the major 18.5-kDa and minor 21.5-kDa isoforms of classic MBP with respect to oligodendrocyte (OLG) proliferation. We have found that, in contrast to 18.5-kDa MBP, 21.5-kDa MBP increases proliferation of early developmental immortalized N19-OLGs by elevating the levels of phosphorylated ERK1/2 and Akt1 kinases and of ribosomal protein S6. Coculture of N2a neuronal cells with N19-OLGs transfected with the 21.5-kDa isoform (or conditioned medium from), but not the 18.5-kDa isoform, caused the N2a cells to have increased neurite outgrowth and process branching complexity. These roles were dependent on subcellular localization of 21.5-kDa MBP to the nucleus and on the exon II-encoded segment, suggesting that the nuclear localization of early minor isoforms of MBP may play a crucial role in regulating and/or initiating myelin and neuronal development in the mammalian CNS.
authors.affiliation: Department of Molecular and Cellular Biology, University of Guelph, Guelph, Ontario, Canada.
authors.forename: Graham S T
authors.initials: GS
authors.lastname: Smith
authors.forename: Bożena
authors.initials: B
authors.lastname: Samborska
authors.forename: Steven P
authors.initials: SP
authors.lastname: Hawley
authors.forename: Jordan M
authors.initials: JM
authors.lastname: Klaiman
authors.forename: Todd E
authors.initials: TE
authors.lastname: Gillis
authors.forename: Nina
authors.initials: N
authors.lastname: Jones
authors.forename: Joan M
authors.initials: JM
authors.lastname: Boggs
authors.forename: George
authors.initials: G
authors.lastname: Harauz
mesh_terms: D000818:Animals; D002461:Cell Line, Transformed; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism*; D002467:Cell Nucleus / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D049109:Cell Proliferation; D018920:Coculture Techniques; D051379:Mice; D008970:Molecular Weight; D004676:Myelin Basic Protein / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D016501:Neurites / Q000737:chemistry / Q000502:physiology*; D009836:Oligodendroglia / Q000737:chemistry / Q000378:metabolism*; D020033:Protein Isoforms / Q000502:physiology
chemical_list: D004676:Myelin Basic Protein; D020033:Protein Isoforms