Phospholipid signalling in the nucleus. Een DAG uit het leven van de inositide signalering in de nucleus.
Diverse methodologies, ranging from activity measurements in various nuclear subfractions to electron microscopy, have been used to demonstrate and establish that many of the key lipids and enzymes responsible for the metabolism of inositol lipids are resident in nuclei. PtdIns(4)P, PtdIns(4,5)P2 and PtdOH are all present in nuclei, as well as the corresponding enzyme activities required to synthesise and metabolise these compounds. In addition other non-inositol containing phospholipids such as phosphatidylcholine constitute a significant percentage of the total nuclear phospholipid content. We feel that it is pertinent to include this lipid in our discussion as it provides an alternative source of 1, 2-diacylglycerol (DAG) in addition to the hydrolysis of PtdIns(4, 5)P2. We discuss at length data related to the sources and possible consequences of nuclear DAG production as this lipid appears to be increasingly central to a number of general physiological functions. Data relating to the existence of alternative pathways of inositol phospholipid synthesis, the role of 3-phosphorylated inositol lipids and lipid compartmentalisation and transport are reviewed. The field has also expanded to a point where we can now also begin to address what role these lipids play in cellular proliferation and differentiation and hopefully provide avenues for further research.
D'Santos
C S
CS
The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
Clarke
J H
JH
Divecha
N
N
D019870:1-Phosphatidylinositol 4-Kinase / Q000378:metabolism; D000818:Animals; D002467:Cell Nucleus / Q000201:enzymology / Q000378:metabolism*; D004075:Diglycerides / Q000096:biosynthesis; D006801:Humans; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D043265:Phosphatidylinositol Diacylglycerol-Lyase; D010716:Phosphatidylinositols / Q000378:metabolism; D054801:Phosphoinositide Phospholipase C; D010743:Phospholipids / Q000378:metabolism*; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D015398:Signal Transduction; D010738:Type C Phospholipases / Q000378:metabolism
C011439:1,2-diacylglycerol; D004075:Diglycerides; D010716:Phosphatidylinositols; D010743:Phospholipids; D019869:Phosphatidylinositol 3-Kinases; D019870:1-Phosphatidylinositol 4-Kinase; D010727:Phosphoric Diester Hydrolases; D010738:Type C Phospholipases; D054801:Phosphoinositide Phospholipase C; D043265:Phosphatidylinositol Diacylglycerol-Lyase