The Structural and Functional Versatility of Inositol Phosphates

Abstract

This review presents a summary of our current knowledge of inositol phosphate turnover in animal cells. In the Figure 1, the various metabolic reactions are sub-divided into several distinct groups; each of these is discussed in turn in this review, in an effort to illustrate the functional versatility of these polyphosphates.The Ins(l,4,5)P 3 / Ins(l,3,4,5)P 4 cycleThe discovery of inositol phosphate-mediated cellular Ca 2+ mobilization was a pivotal development in the field of signal transduction (/), but this breakthrough also owes much to the persistence of some other workers who had the foresight to develop and promote the idea of receptor-activated inositide signaling. It was the Hokins who first discovered that muscarinic agonists accelerate the turnover of Ptdlns in tissue slices from brain and pancreas (2). It was unfortunate that their dedication to characterizing this effect over the following 20 years did not lead them to ascribe its biological function. Indeed, there was little general interest in this so-called "phosphoinositide effect", until Michell (3) proposed that it might drive receptor-dependent Ca 2+ influx into the cell. Later, Michell and his colleagues showed mat an accelerated PtdIns(4,5)P 2 turnover immediately followed receptor-occupation by Ca 2+ -mobilizing hormones (4,5). The modem era of inositide research was now bom: Berridge (6) recognized that the Ins(l,4,5)P 3 formed by hydrolysis of PtdIns(4,5)P 2 was a candidate intracellular signal, and so it was discovered that Ins(l,4,5)/\ released Ca 2+ from endoplasmic reticulum (ER) (7). This intracellular release of Ca was found to be co-ordinated with an increase in the rate of Ca 2+ influx into the cell (7) -which finally confirmed the essence of the original idea (3) that inositol lipid turnover regulated Ca 2+ entry.Ins(l,4,5)P 3 -induced Ca 2+ release mediates an abundance of cellular responses as diverse as fertilization, cell growth and differentiation, neuronal signaling, secretion, and phototransduction. The distinct signaling requirements of individual cells are served by cell-and agonist-specific spatiotemporal patterns of Ca 2+ signaling. These arise not just from the binding of Ins(l,4,5)P 3 to its receptor, but also by modulation of this ligand/protein interaction by both cytosolic and ER-luminal Ca 2+ , and there is also input from the process of Ca 2+ entry, and Ins(l,4,5)P 3 metabolism (8). There is also regulatory diversity between the three major forms of the Ins(l,4,5)P 3 receptors that are currently recognized (see reference 9 for a review).

Oscillatory Chloride Efflux at the Pollen Tube Apex Has a Role in Growth and Cell Volume Regulation and Is Targeted by Inositol 3,4,5,6-Tetrakisphosphate

“…Functional roles for other inositol polyphosphates are emerging (for reviews, see Mennitti et al, 1993;Shears, 1996;Caffrey et al, 1999;Irvine and Schell, 2001). One of these isomers is Ins(3,4,5,6)P 4 , which has been shown to negatively regulate a Ca 2ϩ -activated Cl Ϫ channel that is important for secretion and osmoregulation in epithelial secretory cells (Vajanaphanich et al, 1994;Ismailov et al, 1996;Xie et al, 1996Xie et al, , 1998Barrett et al, 1998;Nilius et al, 1998;Yang et al, 1999;Carew et al, 2000;Ho et al, 2000Ho et al, , 2001.…”