Methacholine and PDGF activate store-operated calcium entry in neuronal precursor cells via distinct calcium entry channels

Abstract

Neurons are a diverse cell type exhibiting hugely different morphologies and neurotransmitter specifications. Their distinctive phenotypes are established during differentiation from pluripotent precursor cells. The signalling pathways that specify the lineage down which neuronal precursor cells differentiate remain to be fully elucidated. Among the many signals that impinge on the differentiation of neuronal cells, cytosolic calcium (Ca2+) has an important role. However, little is known about the nature of the Ca2+ signals involved in fate choice in neuronal precursor cells, or their sources. In this study, we show that activation of either muscarinic or platelet-derived growth factor (PDGF) receptors induces a biphasic increase in cytosolic Ca2+ that consists of release from intracellular stores followed by sustained entry across the plasma membrane. For both agonists, the prolonged Ca2+ entry occurred via a store-operated pathway that was pharmacologically indistinguishable from Ca2+ entry initiated by thapsigargin. However, muscarinic receptor-activated Ca2+ entry was inhibited by siRNA-mediated knockdown of TRPC6, whereas Ca2+ entry evoked by PDGF was not. These data provide evidence for agonist-specific activation of molecularly distinct store-operated Ca2+ entry pathways, and raise the possibility of privileged communication between these Ca2+ entry pathways and downstream processes.

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

“…The store-operated Ca 2+ influx was higher in JOE cells, indicating that the mechanism responsible for the effect of golli on OPC proliferation was mediated through an increase in Ca 2+ influx through SOCCs. Recently, Cuddon et al (2008) reported that PDGF activates store-operated Ca 2+ entry in neuronal precursor cells, a finding that supports our data indicating that store-operated Ca 2+ uptake is an essential component of the PDGF mitotic mechanism in OPCs.…”

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

“…In this paper, we identified the channel responsible for this Ca ++ uptake increase in golli-overexpressing cells and we revealed for the first time that extracellular Ca ++ uptake through TRPC1 is an important component in the mechanism of OPC proliferation. Recently, Cuddon et al (2008) reported that PDGF activates store-operated Ca ++ entry in neuronal precursor cells, a finding that supports our data indicating that SOCCs are essential for neural cell division. Furthermore, several studies have shown that TRPC1 plays a role in Ca ++ influx and smooth muscle cell proliferation (Golovina et al, 2001; Sweeney et al, 2002a, b) and mediates Ca ++ influx activated by basic fibroblast growth factor (bFGF; FGF-2) in endothelial cells (Antoniotti et al, 2002).…”

Platelet-Derived Growth Factor-BB Restores Human Immunodeficiency Virus Tat-Cocaine-Mediated Impairment of Neurogenesis: Role of TRPC1 Channels

“…PDGF is known to exerts its action by triggering [Ca 2+ ]i transients in neuronal precursor cells(Cuddon et al, 2008), however, the mechanism of action remains less clear. Herein we report that PDGF-BB induced [Ca 2+ ]i elevations through activation of TRPC1.…”