Modulation of Canonical Transient Receptor Potential Channel 1 in the Proliferation of Oligodendrocyte Precursor Cells by the Golli Products of the Myelin Basic Protein Gene

Abstract

Golli proteins, products of the myelin basic protein gene, function as a new type of modulator of intracellular Ca²⁺ levels in oligodendrocyte progenitor cells (OPCs). Because of this, they affect a number of Ca²⁺-dependent functions, such as OPC migration and process extension. To examine further the Ca²⁺ channels regulated by golli, we studied the store-operated Ca²⁺ channels (SOCCs) in OPCs and acute brain slice preparations from golli knock-out and golli-overexpressing mice. Our results showed that pharmacologically induced Ca²⁺ release from intracellular stores evoked a significant extracellular Ca²⁺ entry after store depletion in OPCs. They also indicated that, under these pharmacological conditions, golli promoted activation of Ca²⁺ influx by SOCCs in cultured OPCs as well as in tissue slices. The canonical transient receptor potential family of Ca²⁺ channels (TRPCs) has been postulated to be SOCC subunits in oligodendrocytes. Using a small interfering RNA knockdown approach, we provided direct evidence that TRPC1 is involved in store-operated Ca²⁺ influx in OPCs and that it is modulated by golli. Furthermore, our data indicated that golli is probably associated with TRPC1 at OPC processes. Additionally, we found that TRPC1 expression is essential for the effects of golli on OPC proliferation. In summary, our data indicate a key role for golli proteins in the regulation of TRPC-mediated Ca²⁺ influx, a finding that has profound consequences for the regulation of multiple biological processes in OPCs. More important, we have shown that extracellular Ca²⁺ uptake through TRPC1 is an essential component in the mechanism of OPC proliferation.