Multiple kinase pathways regulate voltage-dependent Ca2+ influx and migration in oligodendrocyte precursor cells.

TitleMultiple kinase pathways regulate voltage-dependent Ca2+ influx and migration in oligodendrocyte precursor cells.
Publication TypeJournal Article
Year of Publication2010
AuthorsPaez, PM, Fulton DJ, Spreur V, Handley V, Campagnoni AT
JournalThe Journal of neuroscience : the official journal of the Society for Neuroscience
Date Published2010 May 5
KeywordsAnimals, Animals, Newborn, Benzophenanthridines, Brain, Calcium, Calcium Channel Blockers, Calcium Channels, L-Type, Cell Culture Techniques, Cell Differentiation, Cell Movement, Mice, Oligodendroglia, Platelet-Derived Growth Factor, Potassium, Protein-Serine-Threonine Kinases, Protein-Tyrosine Kinases, Receptor Protein-Tyrosine Kinases, Signal Transduction, Stem Cells, Tetradecanoylphorbol Acetate, Vanadates

It is becoming increasingly clear that voltage-operated Ca(2+) channels (VOCCs) play a fundamental role in the development of oligodendrocyte progenitor cells (OPCs). Because direct phosphorylation by different kinases is one of the most important mechanisms involved in VOCC modulation, the aim of this study was to evaluate the participation of serine-threonine kinases and tyrosine kinases (TKs) on Ca(2+) influx mediated by VOCCs in OPCs. Calcium imaging revealed that OPCs exhibited Ca(2+) influx after plasma membrane depolarization via L-type VOCCs. Furthermore, VOCC-mediated Ca(2+) influx declined with OPC differentiation, indicating that VOCCs are developmentally regulated in OPCs. PKC activation significantly increased VOCC activity in OPCs, whereas PKA activation produced the opposite effect. The results also indicated that OPC morphological changes induced by PKC activation were partially mediated by VOCCs. Our data clearly suggest that TKs exert an activating influence on VOCC function in OPCs. Furthermore, using the PDGF response as a model to probe the role of TK receptors (TKr) on OPC Ca(2+) uptake, we found that TKr activation potentiated Ca(2+) influx after membrane depolarization. Interestingly, this TKr modulation of VOCCs appeared to be essential for the PDGF enhancement of OPC migration rate, because cell motility was completely blocked by TKr antagonists, as well as VOCC inhibitors, in migration assays. The present study strongly demonstrates that PKC and TKrs enhance Ca(2+) influx induced by depolarization in OPCs, whereas PKA has an inhibitory effect. These kinases modulate voltage-operated Ca(2+) uptake in OPCs and participate in the modulation of process extension and migration.

Alternate JournalJ. Neurosci.