Phosphatidylinositol localization

Kitazawa T, Kobayashi S, Horiuti K, Somlyo AV, Somlyo AP 1989 Receptor coupled, permeabilized smooth muscle role of the phosphatidylinositol cascade, G proteins and modulation of the contractile response to Ca2+. J Biol Chem 264 5339-5342 Lopez-Lopez JR, Shacklock PS, Balke CW, Wier WG 1995 Local calcium transients triggered by single L-type calcium channel currents in cardiac cells. Science 268 1042-1045 Marks AR, Fleischer S, Tempst P 1990 Surface topography analysis of the ryanodine receptor/ junctional channel complex based on proteolysis sensitivity mapping. J Biol Chem 265 13143-13149... 

Figure 1. Control of mitochondrial biogenesis by the nuclear genome. Most mitochondrial proteins, including cytochrome c, are nuclear gene products which are subsequently imported into mitochondria. Similarly, most enzymes involved in synthesis of mitochondrial phosphoplipids are encoded in the nuclear genome. Being located in the endoplasmatic reticulum, they synthesize phosphatidylcholine (PtdCho), phosphatidylserine (PtdSer), phosphatidylglycerol (PG) and phosphatidylinositol (Ptdins). The phospholipids are transferred to the outer membrane. The imported lipids then move into the inner membrane at contact sites. Mitochondria then diversify phospholipids. They decarboxylate phosphatidylserine to phosphatidylethanolamine (PtdEtN), but the main reaction is the conversion of imported phosphatidylglycerol to cardiolipin (CL). Cardiolipins localize mainly in the outer leaflet of the inner membrane.

It can be seen from Figure 1 that the choline-containing phospholipids, phosphatidylcholine and sphingomyelin are localized predominantly in the outer monolayer of the plasma membrane. The aminophospholipids, conprising phosphatidylethanolamine and phosphatidylserine, by contrast, are enriched in the cytoplasmic leaflet of the membrane (Bretcher, 1972b Rothman and Lenard, 1977 Op den Kamp, 1979). The transmembrane distribution of the minor membrane lipid components has been determined by reaction with lipid-specific antibodies (Gascard et al, 1991) and lipid hydrolases (Biitikofer et al, 1990). Such studies have shown that phosphatidic acid, phosphatidylinositol and phosphatidylinositol-4,5-fc -phosphate all resemble phosphatidylethanolamine in that about 80% of the phospholipids are localized in the cytoplasmic leaflet of the membrane. 

Klippel A, Reinhard C, Kavanaugh WM, et al. Membrane localization of phosphatidylinositol... 

Zini, N. Ognibene, A. Bavelloni, A. Santi, S. Sabatelli, P. Baldini, N. Scotland , K. Serra, M. Maraldi, N.M. Cytoplasmic and nuclear localization sites of phosphatidylinositol 3-kinase in human osteosarcoma sensitive and multidrug-resistant Saos-2 cells. Histochem. Cell Biol., 106, 457-464 (1996)... 

Volinia, S. Hiles, I. Ormondroyd, E. Nizetic, D. Antonacci, R. Rocchi, M. Waterfield, M.D. Molecular cloning, cDNA sequence, and chromosomal localization of the human phosphatidylinositol 3-kinase pllOa (PIK3CA) gene. Genomics, 24, 472-477 (1994)... 

Prior, LA. Clague, M.J. Localization of a class II phosphatidylinositol 3-kinase, PI3KC2a, to clathrin-coated vesicles. Mol. Cell. Biol., 1, 162-166 (1999)... 

Fig. 3.1 Concentration of two local anesthetics, procaine and dibucaine, displacing, at two different pH values, 50% of the bound calcium from phosphatidylserine (PS) (A) and phosphatidylinositol (PI) (B). Open columns, pH 7.5 dark columns pH 9.5. (Reprinted from Fig. 4 of ref. 10 with permission from Elsevier Science.)...

Botelho, R.J., Teruel, M., Dierckman, R., Anderson, R., Wells, A., York, J.D., Meyer, T., et al. Localized biphasic changes in phosphatidylinositol-4,5-bisphosphate at sites of phagocytosis. J Cell Biol 151 (2000) 1353-1368. 

Watt, S.A., Kular, G., Fleming, I.N., Downes, C.P. and Lucocq, J.M., 2002, Subcellular localization of phosphatidylinositol 4,5-bisphosphate using the pleckstrin homology domain of phospholipase C81. Biochem. J. 363 657-666. 

Takahashi, K., Nakagawa, M., Young, S.G., and Yamanaka, S. (2005). Differential membrane localization of ERas and Rheb, two Ras-related proteins involved in the phosphatidylinositol 3-kinase/mTOR pathway. J Biol Chem 280 32768-32774. 

Phosphatidylinositol 4-phosphate (PI-4-P, 3) is the second most abundant inositol phospholipid in biological membranes. It is a product of phosphorylation by four different species of PI 4-kinases (21), and it is a precursor to PI-4,5-P2 and PI-3,4,5-P3. These kinases are the two inositol lipids whose biological roles are understood best. The biological function of PI-4-P is not well known however, the studies in yeast indicate its role extends beyond the substrate for PI 5-kinase (21), such as regulation of vesicular trafficking and protein secretion from Golgi. PI-4-P is removed by the subsequent phosphorylation to PI-4,5-P2 or dephosphorylation to PI by ER-localized phosphatase (21). 

Local anesthetics have a wide range of effects. They inhibit sodium, potassium, and calcium ion channels, alpha-adrenoceptors, and phosphatidylinositol signalling. They also cause dysrhythmias when injected directly into the brain. Local anesthetics are also mitochondrial poisons and impair oxidative phosphorylation. 

A. The prostanoids have a wide variety of physiologic effects, but they regulate these processes locally by binding to a receptor on the plasma membrane of a cell close to where the prostanoid was synthesized. Binding of the prostanoid to the receptor nsually activates a GTP-binding protein, which acts to activate (or inhibit) adenylate cyclase or the phosphatidylinositol cascade. 

Cooper, P.H. Hawthorne, J.N. Phosphatidylinositol kinase and diphosphoinositide kinase of rat kidney cortex properties and subcellular localization. Biochem. J., 160, 97-105 (1976)... 

Lundberg, G.A. Jergil, B. Sundler, R. Subcellular localization and enzymatic properties of rat liver phosphatidylinositol-4-phosphate kinase. Bio-chim. Biophys. Acta, 846, 379-387 (1985)... 

Homma, K. Terui, S. Minemura, M. Qadota, H. Anraku, Y. Kanaho, Y. Ohya, Y. Phosphatidylinositol-4-phosphate 5-kinase localized on the plasma membrane is essential for yeast cell morphogenesis. J. Biol. Chem., 273, 15779-15786 (1998)... 

Coppolino, M.G. Dierckman, R. Loijens, J. Collins, R.R Pouladi, M. Jong-stra-Bilen, J. Schreiber, A.D. Trimble, W.S. Anderson, R. Grinstein, S. Inhibition of phosphatidylinositol-4-phosphate 5-kinase la impairs localized actin remodeling and suppresses phagocytosis. J. Biol. Chem., 277, 43849-43857 (2002)... 

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