Phospholipid signalling in the nucleus

Diverse methodologies, ranging from activity measurements in various nuclea r subfractions to electron microscopy, have been used to demonstrate and es tablish that many of the key lipids and enzymes responsible for the metabol ism of inositol lipids are resident in nuclei. PtdIns(4)P, PtdIns(4,5)P-2 a nd PtdOH are all present in nuclei, as well as the corresponding enzyme act ivities required to synthesise and metabolise these compounds. In addition other non-inositol containing phospholipids such as phosphatidylcholine con stitute 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)P-2. We discuss at length data related to the sources and possible consequences of nuclear DAG production as this lipid a ppears to be increasingly central to a number of general physiological func tions. Data relating to the existence of alternative pathways of inositol p hospholipid synthesis, the role of 3-phosphorylated inositol lipids and lip id compartmentalisation and transport are reviewed. The field has also expa nded to a point where we can now also begin to address what role these lipi ds play in cellular proliferation and differentiation and hopefully provide avenues for further research. (C) 1998 Elsevier Science B.V. All rights re served.