Journal
JOURNAL OF NEUROSCIENCE
Volume 28, Issue 33, Pages 8326-8337Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.1482-08.2008
Keywords
oligodendrocytes; migration; phosphorylation; Cdk5; WAVE2; CNS
Categories
Funding
- Japanese Ministry of Education, Culture, Sports, Science, and Technology
- Japanese Ministry of Human Health and Welfare
- Japan Society for the Promotion of Science for Young Scientists
- Astellas Metabolic Disease Foundation
- Human Science Foundation
- Kato Memorial Bioscience Foundation
- Takeda Science Foundation
Ask authors/readers for more resources
Myelin formation of the CNS is a complex and dynamic process. Before the onset of myelination, oligodendrocytes (OLs), the myelinforming glia of the CNS, proliferate and migrate along axons. Little is known about the molecular mechanisms underlying the early myelination processes. Here, we show that platelet-derived growth factor (PDGF), the crucial physiological ligand in early OL development, controls the migration of oligodendrocyte precursor cells (OPCs) through cyclin-dependent kinase 5 (Cdk5). PDGF stimulates Cdk5 activity in a time-dependent manner, whereas suppression of Cdk5 by the specific inhibitor roscovitine or by the retrovirus encoding short-hairpin RNA for Cdk5 impairs PDGF-dependent OPC migration. The activation of Cdk5 by PDGF is mediated by the phosphorylation of the nonreceptor tyrosine kinase, Fyn, whose inhibition reduces PDGF-dependent OPC migration. Furthermore, Cdk5 regulates PDGF-dependent OPC migration through the direct phosphorylation of WASP (Wiskott-Aldrich syndrome protein)-family verprolin-homologous protein 2 (WAVE2). Cdk5 phosphorylates WAVE2 at Ser-137 in vitro. Infection of the WAVE2 construct harboring the Ser-137-to-Ala reduces PDGF-dependent migration. Together, PDGF regulates OPC migration through an as-yet-unidentified signaling cascade coupling Fyn kinase to Cdk5 phosphorylation of WAVE2. These results provide new insights into both the role of Cdk5 in glial cells and the molecular mechanisms controlling the early developmental stage of OLs.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available