title: Golli myelin basic proteins regulate oligodendroglial progenitor cell migration through voltage-gated Ca2+ influx.
abstract: Migration of oligodendrocyte progenitor cells (OPCs) from proliferative zones to their final location in the brain is an essential step in nervous system development. Golli proteins, products of the myelin basic protein gene, can modulate voltage-gated Ca(2+) uptake in OPCs during process extension and retraction. Given the importance of process extension/retraction on movement, the consequences of golli expression on OPC migration were examined in vivo and in vitro using time-lapse imaging of isolated OPCs and acute brain slice preparations from golli KO and golli J37 overexpressing mice (JOE). The results indicated that golli stimulated migration, and this enhanced motility was associated with increases in the activity of voltage operated Ca(2+) channels (VOCCs). Activation of VOCCs by high K(+) resulted in a significant increase in the migration speed of JOE OPCs versus control cells and golli-mediated modulation of OPC migration disappeared in the presence of VOCC antagonists. During migration, OPCs generated Ca(2+) oscillations that were dependent on voltage-calcium influx and both the amplitude and frequency of these Ca(2+) transients correlated positively with the rate of cell movement under a variety of pharmacological treatments. The Ca(2+) transient amplitude and the rate of cell movement were significantly lower in KO cells and significantly higher in JOE cells suggesting that the presence of golli promotes OPC migration by increasing the size of voltage-mediated Ca(2+) oscillations. These data define a new molecule that regulates Ca(2+) homeostasis in OPCs, and are the first to demonstrate that voltage-gated Ca(2+) channels can regulate an OPC function, such as migration.
authors.affiliation: Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine at UCLA, Los Angeles Medical School, Los Angeles, California 90095, USA.
authors.forename: Pablo M
authors.initials: PM
authors.lastname: Paez
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Fulton
authors.forename: Vilma
authors.initials: V
authors.lastname: Spreuer
authors.forename: Vance
authors.initials: V
authors.lastname: Handley
authors.forename: Celia W
authors.initials: CW
authors.lastname: Campagnoni
authors.forename: Wendy B
authors.initials: WB
authors.lastname: Macklin
authors.forename: Christopher
authors.initials: C
authors.lastname: Colwell
authors.forename: Anthony T
authors.initials: AT
authors.lastname: Campagnoni
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000502:physiology*; D020013:Calcium Signaling / Q000502:physiology*; D002465:Cell Movement / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D004305:Dose-Response Relationship, Drug; D049452:Green Fluorescent Proteins / Q000235:genetics; D066298:In Vitro Techniques; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008954:Models, Biological; D004676:Myelin Basic Protein; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000502:physiology*; D009836:Oligodendroglia / Q000502:physiology*; D011189:Potassium Chloride / Q000494:pharmacology; D020033:Protein Isoforms / Q000235:genetics; D013234:Stem Cells; D013997:Time Factors; D014157:Transcription Factors / Q000172:deficiency / Q000502:physiology*; D014162:Transfection / Q000379:methods
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; C499047:Mbp protein, mouse; D004676:Myelin Basic Protein; D009419:Nerve Tissue Proteins; D020033:Protein Isoforms; D014157:Transcription Factors; D049452:Green Fluorescent Proteins; D011189:Potassium Chloride; D002118:Calcium