Nuclear phospholipid signaling: phosphatidylinositol-specific phospholipase C and phosphoinositide 3-kinase

Abstract

Over the last 20 years, numerous studies have demonstrated the existence of nuclear phosphoinositide signaling distinct from the one at the plasma membrane. The activation of phosphatidylinositol-specific phospholipase C (PI-PLC) and phosphoinositide 3-kinase (PI3K), the generation of diacylglycerol (DAG) and the accumulation of the 3-phosphorylated phosphoinositides have been documented in the nuclei of different cell types.In this review, we summarize some recent studies of the subnuclear localization, mechanisms of activation and the possible physiological roles of the nuclear PI-PLC and PI-3 kinases in the regulation of cell cycle, survival and differentiation.

Inositol Pyrophosphates Modulate S Phase Progression after Pheromone-induced Arrest in Saccharomyces cerevisiae

“…In S. cerevisiae, there is only one Plc1 encoded by the gene PLC1 (9,10). In mammalian cells, at least 13 Plc isoforms have been identified, and many of them, including Plc-␤, -␥, -␦, and -, have been found to be activated in nuclei of cells at a particular phase of the cell cycle (27). A sole Plc1 in yeasts corresponds best to the mammalian Plc-␦1, and this is the isoform that has been most consistently found to be associated with nuclei of mammalian cells somewhere at the beginning of S phase.…”

“…In synchronized NIH3T3 cells, the level of Plc-␦1 in nuclei increased at the G 1 /S boundary (7), and "knockdown" of Plc-␦1 in rat C6 glioma cells significantly decreased proliferation and delayed the progression through S phase (28). Enhanced degradation of cyclin E levels in mammalian cells (28) has been suggested to mediate the role of Plc in cell cycle control, but it is not clear how the enzyme might interact with the cell cycle machinery to regulate progression through different phases of the cell cycle (9,27).…”

An update on nuclear calcium signalling

“…For example, the ADP-ribosyl cyclase enzyme that is responsible for the production of cyclic ADP ribose (cADPR) and/or NAADP is localised in the nucleus (Adebanjo et al, 1999;Bezin et al, 2008a;Trubiani et al, 2008). In addition, it has been well established that nuclei possess phosphoinositide signalling mechanisms that are similar to, but distinct from, those that occur at the plasma membrane, and which can lead to InsP 3 production (Visnjic and Banfic, 2007;Ye and Ahn, 2008). and phosphoinositide-specific phospholipase C (PtdIns-PLC) (Downes et al, 2005).…”

“…It is known that PtdIns-PLCβ isoforms are activated at the plasma membrane by G-proteincoupled receptors and are responsible for rapid InsP 3 production and acute Ca 2+ signals (see Box 2). In the nucleus, however, PtdIns-PLCβ 1 plays an important role in signalling events that are evoked by growth-factor-receptor stimulation (Visnjic and Banfic, 2007). For example, PtdIns-PLCβ 1 was found to be essential during the differentiation of skeletal muscle myoblasts .…”

Inositol pyrophosphates modulate cell cycle independently of alteration in telomere length

“…However, downstream targets of Plc-generated second messengers in nuclei have remained poorly described (reviewed in Visnjic and Banfic, 2007;Follo et al, 2014). Irvine et al (1993) first observed that there are many similarities between nuclear phospholipid signalling in mammals and phospholipid signalling in the budding yeasts Saccharomyces cerevisiae (Irvine, 2003).…”