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
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Golli proteins, products of the myelin basic protein gene, function as a new type of modulator of intracellular Ca(2+) levels in oligodendrocyte progenitor cells (OPCs). Because of this, they affect a number of Ca(2+)-dependent functions, such as OPC migration and process extension. To examine further the Ca(2+) channels regulated by golli, we studied the store-operated Ca(2+) channels (SOCCs) in OPCs and acute brain slice preparations from golli knock-out and golli-overexpressing mice. Our results showed that pharmacologically induced Ca(2+) release from intracellular stores evoked a significant extracellular Ca(2+) entry after store depletion in OPCs. They also indicated that, under these pharmacological conditions, golli promoted activation of Ca(2+) influx by SOCCs in cultured OPCs as well as in tissue slices. The canonical transient receptor potential family of Ca(2+) 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 Ca(2+) 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 Ca(2+) influx, a finding that has profound consequences for the regulation of multiple biological processes in OPCs. More important, we have shown that extracellular Ca(2+) uptake through TRPC1 is an essential component in the mechanism of OPC proliferation.
|Number of pages||13|
|Journal||The Journal of Neuroscience|
|Publication status||Published - 9 Mar 2011|
- Animals, Blotting, Western, Calcium, Cell Cycle, Cell Proliferation, Cells, Cultured, Cerebral Cortex, Immunohistochemistry, Mice, Mice, Transgenic, Myelin Basic Protein, Nerve Tissue Proteins, Oligodendroglia, Reverse Transcriptase Polymerase Chain Reaction, Stem Cells, TRPC Cation Channels, Transcription Factors