Cdk5 Phosphorylation of WAVE2 Regulates Oligodendrocyte Precursor Cell Migration through Nonreceptor Tyrosine Kinase Fyn

Abstract

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 (

P2X7 receptors and Fyn kinase mediate ATP-induced oligodendrocyte progenitor cell migration

“…There is direct evidence demonstrating that in cultured OPCs stimulated with PDGF, Fyn kinase could promote the migration of OPCs through WAVE2 phosphorylation [32]. Our previous study also demonstrated that Slit2 could regulate the dispersal of OPCs through Fyn and RhoA signaling [31].…”

“…Moreover, P2X7 receptor activation was demonstrated to trigger extracellular calcium ion influx, then activate intracellular kinases, such as MAPK [26,28] and Akt [30], or increase the expression of matrix metalloproteinase 9 [29], thereby facilitating cell migration. Moreover, Fyn kinase, one member of the Src family, is involved in OPC migration [31,32]. In the present study, we examined the effect of a high concentration of ATP on OPCs in vitro, and showed that P2X7 receptors couple to Fyn kinase to mediate ATP-induced migration of OPCs.…”

“…Moreover, Miyamoto et al showed Fyn expression in primary cultured OPCs by using the technique of RT-PCR [32]. In addition, by using western blot and electrophysiological methods, Agresti et al reported the expression of P2X7 receptors in primary cultured OPCs [12].…”

p39, the Primary Activator for Cyclin-dependent Kinase 5 (Cdk5) in Oligodendroglia, Is Essential for Oligodendroglia Differentiation and Myelin Repair

“…Earlier studies demonstrated essential functions of Cdk5 in neuronal migration, neural network formation, and synaptic plasticity in mammalian brains (5). Besides the traditional view of neuronal centric roles of Cdk5, emerging evidence suggests that Cdk5 also governs the development of oligodendroglia progenitor cells (OPCs) (11)(12)(13). Similar to brain neurons, OPCs migrate to distant brain areas and become mature OLs to myelinate neuronal axons (14).…”

“…However, unlike neuronal development in the embryonic brains, the most vigorous OPC development occurs postnatally (14). Loss of Cdk5 function affects OPC migration and differentiation in culture and results in CNS hypomyelination (12,13,15,16). However, molecular mechanisms that regulate Cdk5 function in neurons and OLs remain elusive.…”