Multiple Kinase Pathways Regulate Voltage-Dependent Ca2+Influx and Migration in Oligodendrocyte Precursor Cells
Open Access
- 5 May 2010
- journal article
- Published by Society for Neuroscience in Journal of Neuroscience
- Vol. 30 (18), 6422-6433
- https://doi.org/10.1523/jneurosci.5086-09.2010
Abstract
It is becoming increasingly clear that voltage-operated Ca2+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 Ca2+influx mediated by VOCCs in OPCs. Calcium imaging revealed that OPCs exhibited Ca2+influx after plasma membrane depolarization via L-type VOCCs. Furthermore, VOCC-mediated Ca2+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 Ca2+uptake, we found that TKr activation potentiated Ca2+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 Ca2+influx induced by depolarization in OPCs, whereas PKA has an inhibitory effect. These kinases modulate voltage-operated Ca2+uptake in OPCs and participate in the modulation of process extension and migration.Keywords
This publication has 68 references indexed in Scilit:
- Fibronectin attenuates process outgrowth in oligodendrocytes by mislocalizing MMP-9 activityMolecular and Cellular Neuroscience, 2009
- Golli Myelin Basic Proteins Regulate Oligodendroglial Progenitor Cell Migration through Voltage-Gated Ca2+InfluxJournal of Neuroscience, 2009
- Regulation of Store-Operated and Voltage-Operated Ca2+ Channels in the Proliferation and Death of Oligodendrocyte Precursor Cells by Golli ProteinsASN Neuro, 2009
- Initiation of Oligodendrocyte Progenitor Cell Migration by a PDGF-A Activated Extracellular Regulated Kinase (ERK) Signaling PathwayNeurochemical Research, 2008
- Tyrosine Kinases Act Directly on the α1 Subunit to Modulate Cav2.2 Calcium ChannelsBiochemical and Biophysical Research Communications, 2002
- Neurotrophin-3 (NT-3) modulates early differentiation of oligodendrocytes in rat brain cortical culturesGlia, 1999
- Protein-tyrosine Kinases Activate while Protein-tyrosine Phosphatases Inhibit L-type Calcium Channel Activity in Pituitary GH3 CellsPublished by Elsevier BV ,1996
- Transient reversion of O4+ Galc− oligodendrocyte progenitor development in response to the phorbol ester TPAJournal of Neuroscience Research, 1993
- Age‐dependent decrease of process formation by cultured oligodendrocytes is augmented by protein kinase C stimulationJournal of Neuroscience Research, 1991
- Phorbol ester enhances morphological differentiation of oligodendrocytes in cultureJournal of Neuroscience Research, 1988