Multiple kinase pathways regulate voltage-dependent Ca2+ influx and migration in oligodendrocyte precursor cells.
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.
Paez
Pablo M
PM
Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine at UCLA, Los Angeles, California 90095, USA.
Fulton
Daniel J
DJ
Spreur
Vilma
V
Handley
Vance
V
Campagnoni
Anthony T
AT
D000818:Animals; D000831:Animals, Newborn; D053119:Benzophenanthridines / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000378:metabolism*; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D051379:Mice; D009836:Oligodendroglia / Q000166:cytology / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D020794:Receptor Protein-Tyrosine Kinases / Q000819:agonists / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014638:Vanadates / Q000494:pharmacology
D053119:Benzophenanthridines; D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D010982:Platelet-Derived Growth Factor; D014638:Vanadates; C016299:chelerythrine; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases; D017346:Protein Serine-Threonine Kinases; D013755:Tetradecanoylphorbol Acetate; D011188:Potassium; D002118:Calcium
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