Regulation of Store-Operated and Voltage-Operated Ca²⁺ Channels in the Proliferation and Death of Oligodendrocyte Precursor Cells by Golli Proteins

Abstract

OPCs (oligodendrocyte precursor cells) express golli proteins which, through regulation of Ca2+ influx, appear to be important in OPC process extension/retraction and migration. The aim of the present study was to examine further the role of golli in regulating OPC development. The effects of golli ablation and overexpression were examined in primary cultures of OPCs prepared from golli-KO (knockout) and JOE (golli J37-overexpressing) mice. In OPCs lacking golli, or overexpressing golli, differentiation induced by growth factor withdrawal was impaired. Proliferation analysis in the presence of PDGF (platelet-derived growth factor), revealed that golli enhanced the mitogen-stimulated proliferation of OPCs through activation of SOCCs (store-operated Ca2+ channels). PDGF treatment induced a biphasic increase in OPC intracellular Ca2+, and golli specifically increased Ca2+ influx during the second SOCC-dependent phase that followed the initial release of Ca2+ from intracellular stores. This store-operated Ca2+ uptake appeared to be essential for cell division, since specific SOCC antagonists completely blocked the effects of PDGF and golli on OPC proliferation. Additionally, in OPCs overexpressing golli, increased cell death was observed after mitogen withdrawal. This phenomenon could be prevented by exposure to VOCC (voltage-operated Ca2+ channel) blockers, indicating that the effect of golli on cell death involved increased Ca2+ influx through VOCCs. The results showed a clear effect of golli on OPC development and support a role for golli in modulating multiple Ca2+-regulatory events through VOCCs and SOCCs. Our results also suggest that PDGF engagement of its receptor resulting in OPC proliferation proceeds through activation of SOCCs.

Impact of Simulated Microgravity on Oligodendrocyte Development: Implications for Central Nervous System Repair

“…Cell cycle time was defined as the period between when a cell was first generated by cytokinesis and when that cell subsequently divided, giving birth to two daughter cells. The time at which cytokinesis occurred was considered to be the first appearance of a distinct border between two daughter cells in videomicroscopic image sequence [14]. Examples of cytokinetic events in GFP-labeled OPCs grown for 24 h on 0G are shown in Figure 2A .…”

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

“…We have found that the golli proteins function as new and novel modulators of intracellular Ca ++ levels in oligodendrocyte progenitor cells (OPCs), T-cells and probably neurons (Feng et al, 2006; Paez et al, 2007, 2009a, b). To characterize further the Ca ++ channels regulated by golli we examined the contribution of store-operated Ca ++ entry in OPCs cultured from golli KO and JOE mice.…”

“…Golli regulates oligodendrocyte progenitor cell (OPC) process extension and differentiation in vitro (Paez et al, 2009a; 2009b), and studies of golli-KO and golli-overexpressing (JOE) brains indicate this influence on OPC development has important consequences for myelination in vivo (Jacobs et al, 2005; 2009). The golli-KO animals exhibit widespread hypomyelination, with particularly striking myelin deficits in the visual and somatosensory cortex, and the optic nerve.…”

“…Recent findings have clearly established that golli protein plays a critical role in regulating Ca ++ influx in OPCs (Paez et al, 2007; 2009a; 2009b; Fulton et al, 2010). …”

TRP Channels Coordinate Ion Signalling in Astroglia

“…This SOCE pathway is functioning in virtually all types of neuroglial cells (Hartmann and Verkhratsky 1998; Malarkey et al 2008; Moller et al 1997; Muller et al 2013; Paez et al 2009; Pivneva et al 2008; Pizzo et al 2001; Reyes and Parpura 2009; Toescu et al 1998; Tuschick et al 1997). To the best of our knowledge, characteristic I CRAC channels have not been hitherto recorded from mature astrocytes and evidence about functional operation of Orai/STIM complex derives from neo-plastic cell lines and astrocytes in vitro (Moreno et al 2012; Motiani et al 2013).…”