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 Ca++ levels in oligodendrocyte progenitor cells (OPCs). Because of this, they affect a number of Ca++ dependent functions such as OPC migration and process extension. To examine further the Ca++ channels regulated by golli, we studied the store operated Ca++ channels (SOCCs) in OPCs and acute brain slice preparations from golli-KO and golli-overexpressing mice. Our results showed that pharmacologically-induced Ca++ release from intracellular stores evoked a significant extracellular Ca++ entry after store depletion in OPCs. They also indicated that under these pharmacological conditions golli promoted activation of Ca++ influx by SOCCs in cultured OPCs as well as in tissue slices. The Canonical TRP (Transient Receptor Potential) family of Ca++ channels (TRPCs) has been postulated to be SOCC subunits in oligodendrocytes. Using a siRNA knock down approach, we provided direct evidence that TRPC1 is involved in store-operated Ca++ 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++ influx, a finding that has profound consequences for the regulation of multiple biological processes in OPCs. More important, we have shown that extracellular Ca++ uptake through TRPC1 is an essential component in the mechanism of OPC proliferation.

Electrophysiological properties of NG2 + cells: Matching physiological studies with gene expression profiles

“…The family can be divided into three subfamilies: the classic/canonical TRPs (TRPCs), the vanilloid receptor-related TRPs (TRPVs), and the melastatin-related TRPs (TRPMs). Several TRP channels are known to be expressed in glial cells: TRPC1 and TRPC3, nonselective cation channels activated by the phospholipase C signaling cascade, have been found in NG2 + cells and oligodendrocytes, respectively (Fusco et al, 2004; Paez et al, 2011; Weerth et al, 2007). TRPM3, a nonspecific cation channel activated by hypotonicity and sphingosine, has been found in both NG2 + cells and oligodendrocytes (Hoffmann et al, 2010).…”

Transient Receptor Potential Channels and Their Role in Modulating Radial Glial–Neuronal Interaction: A Signaling Pathway Involving mGluR5

“…TRPC1 and TRPC4 have been reported to regulate neurite extension in human embryonic stem cell-derived neurons [11]. A TRPC1-mediated increase in calcium entry has been shown to be required for the proliferation of adult hippocampal neural progenitor cells (NPCs) [12] as well as mediating a role in the proliferation of oligodendrocyte progenitor cells [13].…”

Migrating Oligodendrocyte Progenitor Cells Swell Prior to Soma Dislocation

“…It has been reported that both increases and decreases of the basal internal calcium level impair the migration of OPCs49 and that the migration correlates with internal calcium transients50. Furthermore, the golli proteins which regulate the migration of OPCs also regulate the expression of the TRP family member TRPC 151 which is proposed to be a component of store operated calcium channels52.…”