Phospholipase C-eta Enzymes as Putative Protein Kinase C and Ca&lt;sup&gt;2+&lt;/sup&gt; Signalling Components in Neuronal and Neuroendocrine Tissues

Stewart, Alan J. A.; Morgan, Kevin; Farquharson, Colin; Millar, Robert P.

doi:10.1159/000107795

Cited by 53 publications

(20 citation statements)

References 78 publications

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“…They show highest expression in the brain and they are structurally related to PLC␦1 (FIGURE 9). In addition to the usual domains present in PLCs, they have a serine-and proline-rich region and a PDZ-domain interacting sequence in their COOH termini (1470). Relatively little is known about the regulation of these enzymes.…”

Section: F Plcmentioning

confidence: 99%

Phosphoinositides: Tiny Lipids With Giant Impact on Cell Regulation

Balla

2013

Physiological Reviews

1,396

1,655

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Phosphoinositides (PIs) make up only a small fraction of cellular phospholipids, yet they control almost all aspects of a cell's life and death. These lipids gained tremendous research interest as plasma membrane signaling molecules when discovered in the 1970s and 1980s. Research in the last 15 years has added a wide range of biological processes regulated by PIs, turning these lipids into one of the most universal signaling entities in eukaryotic cells. PIs control organelle biology by regulating vesicular trafficking, but they also modulate lipid distribution and metabolism via their close relationship with lipid transfer proteins. PIs regulate ion channels, pumps, and transporters and control both endocytic and exocytic processes. The nuclear phosphoinositides have grown from being an epiphenomenon to a research area of its own. As expected from such pleiotropic regulators, derangements of phosphoinositide metabolism are responsible for a number of human diseases ranging from rare genetic disorders to the most common ones such as cancer, obesity, and diabetes. Moreover, it is increasingly evident that a number of infectious agents hijack the PI regulatory systems of host cells for their intracellular movements, replication, and assembly. As a result, PI converting enzymes began to be noticed by pharmaceutical companies as potential therapeutic targets. This review is an attempt to give an overview of this enormous research field focusing on major developments in diverse areas of basic science linked to cellular physiology and disease.

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Section: F Plcmentioning

confidence: 99%

Phosphoinositides: Tiny Lipids With Giant Impact on Cell Regulation

Balla

2013

Physiological Reviews

1,396

1,655

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“…This was likely due to a Ca 2+ -induced increase in basal PLC activity. Although PLCη2 is not endogenously expressed in COS7 cells (Stewart et al, 2007), multiple PLCs are present in most cell types. Increased intracellular Ca 2+ levels would likely enhance basal activity as Ca 2+ is required for both catalysis and membrane binding.…”

Section: Ef-loop 1 Is Important For Plcη2 Activitymentioning

confidence: 99%

A Canonical EF‐Loop Directs Ca²⁺‐Sensitivity in Phospholipase C‐η2

Popovics

Kamil

Morgan

et al. 2014

J of Cellular Biochemistry

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Phospholipase C-ɳ(PLCɳ) enzymes are a class of phosphatidylinositol 4,5-bisphosphatehydrolyzing enzymes involved in intracellular signaling. PLCɳ2 can sense Ca 2+ (stimulated bỹ 1 µM free Ca 2+ ) suggesting that it can amplify transient Ca 2+ signals. PLCɳ enzymes possess an EF-hand domain composed of two EF-loops; a canonical 12-residue loop (EF-loop 1) and a non-canonical 13-residue loop (EF-loop 2). Ca 2+ -binding to synthetic peptides corresponding to EF-loops 1 and 2 of PLCɳ2 and EF-loop 1 of calmodulin (as a control) was examined by 2D-[ 1 H, 1 H] TOCSY NMR. Both PLCɳ2 EF-loop peptides bound Ca 2+ in a similar manner to that of the canonical calmodulin EF-loop 1, particularly at their N-terminus. A molecular model of the PLCɳ2 EF-hand domain, constructed based upon the structure of calmodulin, suggested both EF-loops may participate in Ca 2+ -binding. To determine whether the EF-hand is responsible for Ca 2+ -sensing, inositol phosphate accumulation was measured in COS7 cells transiently expressing wild-type or mutant PLCɳ2 proteins. Addition of 70µM monensin (a Na + /H + antiporter that increases intracellular Ca 2+ ) induced a 4 to 7-fold increase in wild-type PLCɳ2 activity. In permeabilized cells, PLCn2 exhibited a ~4-fold increase in activity in the presence of 1 µM free Ca 2+ . The D256A (EF-loop1) mutant exhibited a ~10-fold reduction in Ca 2+ -sensitivity and was not activated by monensin, highlighting the involvement of EF-loop 1 in Ca 2+ -sensing. Involvement of EF-loop 2 was examined using D292A, H296A, Q297A and E304A mutants. Interestingly, the monensin responses and Ca 2+ -sensitivities were largely unaffected by the mutations, indicating that the non-canonical EF-loop 2 is not involved in Ca 2+ -sensing.

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“…In mammals, PLCH1 is expressed mainly in neuronal tissue and similar to the other 5 classes of PLC isozymes is involved in protein kinase C activation and calcium metabolism. Since its discovery in 2005, most studies have focused on its role in neurons (Stewart et al, 2007) and this is first report to show that PLCH1 is expressed in the Müllerian duct during the development. What the functional role may be requires further investigation.…”

Section: Discussionmentioning

confidence: 98%

“…VCP belongs to AAA (ATPases associated with various cellular activities) family, and is essential for a wide variety of cellular functions such as ubiquitin/ proteasom-dependent protein degradation, membrane fusion, cell cycle regulation, and endoplasmic reticulum-associated degradation (Latterich et al, 1995, Zhang et al, 2000, Dai and Li, 2001, Ye et al, 2003, Wang et al, 2004, Vandermoere et al, 2006. Expression of VCP mRNA was female specific as PLCH1 is a recently discovered class of isoforms of phospholipase C (PLC) that is involved in the inocitol signaling pathway (Nakahara et al, 2005, Stewart et al, 2007. In females, the expression of PLCH1 mRNA increased in the Müllerian duct at day 9 of incubation to significantly higher levels than that observed in the males.…”

Section: Discussionmentioning

confidence: 99%

Identification of differentially expressed genes involved in the regression and development of the chicken Mllerian duct

Ha¹,

Tsukada²,

Sakai³

et al. 2008

Int. J. Dev. Biol.

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Müllerian ducts of male chickens undergo regression around day 12 of incubation, but the underlining mechanisms remain unclear. The purpose of this study was to identify factors that contribute to regression of the Müllerian duct in the chicken. We first employed annealing control primer-based RT-PCR to screen candidate genes differentially expressed in the Müllerian ducts between male and female. Four differentially expressed genes (MSX2, GAL10, VCP and PLCH1) were partially sequenced. The expression of mRNA of the latter genes and MSX1 in the male and female Müllerian ducts were compared at 7.5, 8 and 9 days of incubation using semiquantitative RT-PCR. The results indicated that both MSX1 and MSX2 mRNA was highly expressed in the male Müllerian duct at day 9 of incubation, whereas, PLCH1 mRNA was lower in the male duct at day 9 of incubation compared to that of the female duct. Although VCP mRNA was expressed in both left and right female Müllerian ducts, no expression was detected in the male duct. Whole mount in situ hybridyzation analysis showed that the expression of MSX1 and MSX2 mRNA were localized specifically in the mesenchymal cells of the male Müllerian duct at day 9 of incubation. In contrast, VCP mRNA expression was observed in both mesenchymal and epithelial cells of the female Müllerian duct but not detected in the male duct. These results suggest that both up-regulation of MSX1 and MSX2 mRNA expression is involved in the regression of the Müllerian duct in male chicken embryo, whereas VCP expression is involved in development of the female duct.

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Phospholipase C-eta Enzymes as Putative Protein Kinase C and Ca<sup>2+</sup> Signalling Components in Neuronal and Neuroendocrine Tissues

Cited by 53 publications

References 78 publications

Phosphoinositides: Tiny Lipids With Giant Impact on Cell Regulation

Phosphoinositides: Tiny Lipids With Giant Impact on Cell Regulation

A Canonical EF‐Loop Directs Ca²⁺‐Sensitivity in Phospholipase C‐η2

Identification of differentially expressed genes involved in the regression and development of the chicken Mllerian duct

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Phospholipase C-eta Enzymes as Putative Protein Kinase C and Ca<sup>2+</sup> Signalling Components in Neuronal and Neuroendocrine Tissues

Cited by 53 publications

References 78 publications

Phosphoinositides: Tiny Lipids With Giant Impact on Cell Regulation

Phosphoinositides: Tiny Lipids With Giant Impact on Cell Regulation

A Canonical EF‐Loop Directs Ca2+‐Sensitivity in Phospholipase C‐η2

Identification of differentially expressed genes involved in the regression and development of the chicken Mllerian duct

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A Canonical EF‐Loop Directs Ca²⁺‐Sensitivity in Phospholipase C‐η2