Phosphoinositides - Key players in cell signalling, in time and space

Over the last few years, many reports have extended our knowledge of the in ositol lipid metabolism and brought out some exciting information about the location, the variety and the role of phosphoinositides (PIs). Besides the so-called "canonical PI pathway" leading to the production of phosphatidyl inositol 4,5-bisphosphate (PtdIns(4,5)P-2), the precursor of the intracellu lar second messengers inositol 1,4,5- trisphosphate and diacylglycerol (DAG ), many other metabolic pathways have been identified to produce seven diff erent polyphosphoinositides. Several of these quantitatively minor lipid mo lecules appear to be specifically involved in the control of cellular event s, such as the spatial and temporal organisation of key signalling pathways , the rearrangement of the actin cytoskeleton or the intracellular vesicle trafficking. This is consistent with the fact that many of the enzymes, suc h as kinases and phosphatases, involved in the tight control of the intrace llular level of polyphosphoinositides, are regulated and/or relocated throu gh cell surface receptors for extracellular ligands. The remarkable feature of PIs, which can be rapidly synthesised and degraded in discrete membrane domains or even subnuclear structures, places them as ideal regulators and integrators of very dynamic mechanisms of cell regulation. In this review we will summarise recent studies on the potential location, the metabolic p athways and the role of the different PIs. Some aspects of the temporal syn thesis of D3 PIs will also be discussed. (C) 2001 Elsevier Science Inc. All rights reserved.