Diacylglycerols and phosphatidates: which molecular species are intracellular messengers?

Caenorhabditis elegans mboa-7, a Member of the MBOAT Family, Is Required for Selective Incorporation of Polyunsaturated Fatty Acids into Phosphatidylinositol

“…We also found that mboa-7 mutants showed defects in early larval development and egg-laying behavior, indicative of the importance of specific PI molecular species in certain physiological functions. It has been assumed that specific PI molecular species are critical for normal phosphoinositide function (Hodgkin et al, 1998;Arnhold et al, 1999;Shirai et al, 1999), which plays important roles in signal transduction, such as the phospholipase C-signaling pathway (Rebecchi and Pentyala, 2000;Rhee, 2001). Interestingly, mutants of egl-8, a phospholipase C isoform in C. elegans, exhibit egglaying defects similar to that observed in our mboa-7 mutants (Trent et al, 1983, Lackner et al, 1999.…”

Activation of phospholipase D by metabotropic glutamate receptor agonists in rat cerebrocortical synaptosomes

“…The regulation of PLD can have important consequences because it generates two di erent second messengers (DAG and PA), each with its own signalling potential (English, 1996;Exton, 1997;Hodgkin et al, 1998). In particular, DAGs derived from PI or PC appear to di er in their ability to induce the translocation of selective PKC isoforms and the time scale of the PKC activation (Ha & Exton, 1993).…”

“…The sequence and distribution of two PLD isoforms, PLD1 and PLD2, have been reported (Colley et al, 1997;Exton, 1998) PLD1 has a low basal activity and can be regulated by PKC, PtdIns(4,5)P 2 and small GTPbinding proteins (Exton, 1998) and PLD2 has a high basal activity and can be activated by fatty acids (Kim et al, 1999). The lipid product of PLD activity, PA, itself can induce a number of cellular functions and it can be converted by PA phosphohydrolase (PAP) into DAG, which is an activator of PKC (Chen et al, 1997;Hodgkin et al, 1998;Nishizuka, 1995). While it is possible that PLD activation requires a coordinated cross-talk between those signalling molecules, there is strong evidence that the activation of small G-proteins and PKC can occur independently of each other.…”

“…Furthermore, the selective coupling between PLD and the stimulation of mGluR subtypes, together with a potential role for PLD in secretion (Williger et al, 1999;Zheng et al, 1997), may also indicate that PLD activation is involved in synaptic plasticity and may therefore play a role in the learning and memory process. Indeed it has been proposed that activation of PLD, which can occur secondary to PI-PLC activation, is a more sustainable signalling pathway when compared with PI turnover (Hodgkin et al, 1998;Klein et al, 1995;Nishizuka, 1995) and the distinct time scale of these signalling events suggests it may be involved in the process of long term potentiation. However, in order to ascribe the action of PLD to such a functional role in synaptic plasticity, the mechanisms controlling its activation, and the subtypes of mGluR involved, require clari®cation.…”

Roles of brain phosphatidylinositol-specific phospholipase C and diacylglycerol lipase in centrally administered histamine-induced adrenomedullary outflow in rats

“…Phospholipase D (PLD) has also been reported to be involved in the production of arachidonic acid. PLD-derived phosphatidate is subsequently transformed by phosphatidate phosphohydrolase into diacylglycerol, which can be further converted to arachidonic acid (Hodgkin et al, 1998;18 Carrasco and Merida, 2007). In fact, PLD-phosphatidate phosphohydrolase pathway was reported to be a source of diacylglycerol and arachidonic acid in rat osteoblast-like cells (Kaneki et al, 1998) and cultured vascular smooth muscle cells (Freeman, 2000).…”