Characterization of Sema5A/plexin-B3 signaling in the oligodendrocyte cell line OLN-93

Abstract

Semaphorins are secreted or transmembrane proteins implicated in variousphysiological processes such as axon guidance, cell motility and attachment, vasculargrowth, immune cell regulation, and tumour progression. Many of these functions aremediated through plexins, the main receptors for semaphorins. While accumulatingevidence suggests the regulation of Rho family GTPases as the common signalingmechanisms mediated by different plexins upon semaphorin stimulation, thesubtype-specific functions of each semaphorin/plexin interaction remains largelyunknown. In this project, we characterized the role of plexin-B3 in oligodendrocytedevelopment using an oligodendroglia cell line OLN-93 that endogenously expressesthis molecule. Our studies revealed that OLN-93 migration is inhibited uponstimulation by Sema5A, the putative ligand of plexin-B3. Sema5A also promotesoutgrowth and branching of cellular process of OLN-93, which is reminiscent ofmorphological differentiation and maturation of oligodendrocyte precursors. Theseeffects were confirmed to be mediated through plexin-B3 by overexpression anddominant negative approaches. Analysis of the signaling pathways in OLN-93 cellsupon Sema5A stimulation revealed that the RhoGTPase family member Cdc42 isactivated, which is accompanied by a redistribution of CNPase to cell periphery andprotrusions. These represent potential mechanisms underlying the induction ofmorphologic differentiation by Sema5A/plexin-B3 interaction.