Increased expression of golli myelin basic proteins enhances calcium influx into oligodendroglial cells

The myelin basic protein (MBP) gene encodes two families of proteins: the classic MBP constituents of myelin and the golli-MBPs, the function of which is less well understood. Previous work suggests that golli proteins may play a role in Ca²⁺ homeostasis in oligodendrocytes (OLs) and in T-cells. Overexpression of golli in OL cell lines induces elaboration of sheets and processes. Live imaging of these cells revealed a rapid retraction of the processes and sheets after depolarization with high K⁺. This phenomenon was associated with a significant increase in [Ca²⁺] _int without changes in cell viability. The results indicated that golli produced its effect through Ca²⁺ influx, rather than Ca ²⁺ release from intracellular stores. Furthermore, a specific [Ca²⁺]_int chelator (BAPTA) or Cd²⁺, a specific blocker of voltage-operated Ca²⁺ channels, abolished the ability of golli to promote process extension in a dose-dependent manner. Analysis of the golli protein identified a myristoylation site at the C terminus of the golli domain, which was essential for the action of golli on Ca²⁺ influx, suggesting that binding of golli to the plasma membrane is important for modulating Ca²⁺ homeostasis. High-resolution spatiotemporal analysis along N19 processes revealed higher-amplitude local Ca²⁺ influx in regions with elevated levels of golli. These findings suggest a key role for golli proteins in regulating voltage-gated Ca²⁺ channels in OLs during process remodeling. Our observations are consistent with the hypothesis that golli proteins, as a part of a protein complex, modulate Ca²⁺ influx at the plasma membrane and along OL processes.