Transformations of phosphatidylinositol phosphates in the outer and inner nuclear membrane are linked to synthesis and restitution of cellular membranes
Amalia Slomiany, Bronislaw L. Slomiany
DOI: 10.4236/health.2011.34035   PDF   HTML     4,352 Downloads   8,176 Views   Citations


The ultimate goal in phosphoinositides cellular metabolism is to decipher their global functional organization and coordination of the com- partmentalized signaling processes. In this report we present evidence linking nuclear phos- phoinositides cycle with endoplasmic reticulum synthesis and function. The rapid transformation of [3H]inositol-labeled phosphoinositides in the intact nuclei (IN) was captured in chase studies for 0-5 min, followed by examination of phosphatidylinositides in the inner nuclear me- mbrane (INM), the outer nuclear membrane (ONM) and endoplasmic reticulum (ER). We revealed that synthesis of phosphatidylinositol phosphates (PIPs) occurs in ONM and the de- phosphorylation takes place in the INM. The rapid transformation of the radiolabeled PIPs in ONM reverberated in their appearance and successive transformation in INM, and in the 5min chased nuclei was tracked to ONM as the re- emerging radiolabeled phosphatidylinositol (PI). These chase-uncovered changes in ONM and INM PIPs profiles allow us to conclude that the observed conversions in the nuclear membrane continuum are induced by the lateral movement of the membrane and its transit from the cytosolic to nuclear and back to cytosolic environment. The suggested membrane synthesisinduced movement provides the means to transport the membrane- and the membrane lipid ligand-associated cytosolic proteins to the intranuclear spaces and renewal of INM. Export of the nuclear components interacting with the modified INM, by exiting from nuclear to cytosolic site, endows ER with a steady influx of the membrane that is conditioned to generate vesicles according to the nucleus delivered templates.

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Slomiany, A. and Slomiany, B. (2011) Transformations of phosphatidylinositol phosphates in the outer and inner nuclear membrane are linked to synthesis and restitution of cellular membranes. Health, 3, 187-199. doi: 10.4236/health.2011.34035.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] Di Paolo, G. and De Camilli, P. (2006) Phosphoinositides in cell regulation and membrane dynamics. Nature, 443, 651-657. doi:10.1038/nature05185
[2] Vicinanza, M., D’Angelo, G., Di Campli, A. and De Matteis, M. A. (2008) Function and disfunction of the PI system in membrane trafficking. EMBO J., 27, 2457- 2470. doi:10.1038/emboj.2008.169
[3] Sasaki, T., Sasaki, J., Sakai, T., Takasuga, S., and Suzuki, A. (2007) The physiology of phosphoinositides. Biological & Pharmaceutical Bulletin, 30, 1599-1604. doi:10.1248/bpb.30.1599
[4] Sasaki, T., Takasuga, S., Sasaki, J., Kofuji, S., Eguchi, S., Yamazaki, M. and Suzuki, A. (2009) Mammalian phosphoinositide kinases and phosphatases. Progress in Lipid Research, 48, 307-343. doi:10.1016/j.plipres.2009.06.001
[5] Barlow, C.A., Laishram, R.S., and Anderson, R.A. (2009) Nuclear Phosphoinositides: a signaling enigma wrapped in a compartmental conundrum. Trends in Cell Biology, 20, 25-35. doi:10.1016/j.tcb.2009.09.009
[6] Boronenkov I,V. Loijens, J.C., Umeda, M., and Anderson, R.A. (1998) Phosphoinositide signaling pathways in nuclei are associated with nuclear specles containing pre-mRNA processing factors. Molecular Biology of the Cell, 9, 3547-3560.
[7] Slomiany, A., Grzelinska, E., Grabska, M., Yamaki, K., Tamura, S. and Slomiany, B.L. (1992) Intracellular processes associated with glycoprotein transport and processing. Archives of Biochemistry and Biophysics, 298, 167-175. doi:10.1016/0003-9861(92)90108-9
[8] Slomiany, A., Grabska M., Piotrowski, E., Morita, M. and Slomiany, B.L. (1994) Intracellular processes associated with vesicular transport from endoplasmic reticulum to Golgi and exocytosis; Ethanol-induced changes in membrane biogenesis. Archives of Biochemistry and Biophysics, 310, 247-255. doi:10.1006/abbi.1994.1164
[9] Slomiany, A., Sano, S., Grabska, M., Yamaki, K. and Slomiany, B.L. (2004) Gastric mucosal cell homeostatic physiome. Critical role of ER-initiated membrane restitution in the fidelity of cell function renewal. Journal of Physiology and Pharmacology, 55, 837-860. 15
[10] Gonzales, M.L. and Anderson, R.A. (2006) Nuclear phosphoinositides kinases and inositol phospholipids. Journal of Cell Biochemistry, 97, 252-260. doi:10.1002/jcb.20655
[11] Irvine, R.F. (2003) Nuclear lipid signaling. Nature Reviews Molecular Cell Biology, 4, 349-361. doi:10.1038/nrm1100
[12] Ruault, M., Dubarry, M. and Taddei, A. (2008) Re-positioning genes to nuclear envelope in mammalian cells; impact on transcription. Trends in Genetics, 24, 574-581. doi:10.1016/j.tig.2008.08.008
[13] Akhtar, A. and Gasser, S.M. (2007), The nuclear envelope and transcriptional control. Nature Reviews Genetics, 8, 507-517. doi:10.1038/nrg2122
[14] Moore, M.J. and Proudfoot, N.J. (2009) Pre-mRNA processing reaches back to transcription and ahead of translation, Cell, 136, 688-700. doi:10.1016/j.cell.2009.02.001
[15] Slomiany, A., Grabska, M. and Slomiany, B.L. (2006) Homeostatic restitution of cell membranes. Nuclear membrane lipid biogenesis and transport of protein from cytosol to intranuclear spaces. International Journal of Biological Sciences, 2, 216-226.
[16] Slomiany, A., Nowak, P., Piotrowski, E. and Slomiany, B.L. (1998) Effect of ethanol on intracellular vesicular transport from Golgi to apical cell membrane: Role of phosphatidylinositol 3-kinase and phospholipase A2 in Golgi vesicles association and fusion with the apical membrane, Alcoholism: Clinical and Experimental Research, 22, 167-175. doi:10.1111/j.1530-0277.1998.tb03634.x
[17] Slomiany, A. and Slomiany, B.L. (2010) Cell membranes composition is defined in ER and their restitution proceeds by en bloc fusion of ER generated transport vesicles. Health, 2, 1444-1454. doi:10.4236/health.2010.212214
[18] Bunce, M.W., Bergendahl, K. and Anderson, R.A. (2006) Nuclear PI(4,5)P2 : Anew place for an old signal. Biochemica et Biophysica Acta, 1761, 560-569.
[19] Garnier-Lhomme, M., Byrne, R.D., Hobday, T.M.C., Gschmeissner, S., Woscholski, R.,Poccia, D.L., Dufourc, E.J., and Larijani, B. (2009) Nuclear envelope remnants: fluid membranes enriched in sterols and phosphatidylinositides. PloS ONE 4, e4255. 16
[20] Tanaka, K., Horiguchi, K., Yoshida,T., Fujisawa, H., Takeuchi, K., Umeda,, M., Kato, S., Ihara, S., Nagata, S. and Fukui, Y. (1999) Evidence that 3,4,5- triphosphate –binding protein can function in nucleus. Journal. Biological Chemistry, 274, 3919-3922. doi:10.1074/jbc.274.7.3919
[21] Ye, K. and Ahn, J.Y. (2008) Nuclear phosphoinositides signaling. Frontiers in Biosciences, 13, 540-548. doi:10.2741/2699
[22] Osborne, S.L., Thomas, C.L., Gschmeissner, S. and Schiavo, G. (2001) Nuclear PtdIns(4,5)P2 assembles in a mitotically regulated particle involved in pre-mRNA splicing. Journal of Cell Science, 114, 2501-2511.
[23] Gozani, O.,Karuman, P., Jones, D.R., Lugovskoy, A.A., Baird, C.L, Zhu,H., Field, S.J.,Lessnick, S.L., Villasenor, J.,Mehrotra, B., Chen, J., Rao, V.R., Brugge, J.S., Ferguson, C,G., Payrastre. B., Myszka, D.G., Cantley, L.C., Wagner, G., Divecha, N. Prestwich, G.D. and Yuan, J. (2003) The PHD finger of the chromatin associated protein ING2 functions as a nuclear phosphoinositides receptor. Cell, 114, 99-111. doi:10.1016/S0092-8674(03)00480-X
[24] Macbeth, M.R., Schubert, H. L., VanDemark, A.P., Lingam, A.t., Hill, C.P. and Bass, B.L. (2005) Inositolhexakisphosphate is bound in ADAR2 core and required for RNA editing. Science, 309, 1534-1539. doi:10.1126/science.1113150
[25] Yu, H., Fukami, K., Watanabe, Y., Ozaki, C. and Takenawa, T. (1998) Phosphatidylinositol 4,5-bisphosphate reverses the inhibition of RNA transcription caused by histone H1. European Journal of Biochemistry, 251, 281-287. doi:10.1046/j.1432-1327.1998.2510281.x
[26] Zhao, K., Wang, W., Rando, O.J., Xue, Y., Swiderek, K., Kuo, A. and Crabtree, G.R. (1998) Rapid and phosphatidylinositol-dependent binding of the SWI/SNFlike BAF complex to chromatin after T lymphocyte receptor signaling. Cell, 95, 625-636. doi:10.1016/S0092-8674(00)81633-5
[27] Mellman, D.L., Gonzales, M.L., Song, C., Barlow, C.A., Wang, P., Kendziorski, C., and Anderson, R.A. (2008) A PtdIns4,5 P2-regulated nuclear poly(A) polymerase controls expression of select mRNAs. Nature, 451, 1013-1017.
[28] Slomiany, A., Tamura, S., Grzelinska, E.,Piotrowski, J., and Slomiany, B.L. (1992) Characterization of the ‘link’ component of submandibular mucus glycoprotein, International Journal of Biochemistry, 24, 1003-1015. doi:10.1016/0020-711X(92)90111-D
[29] Slomiany, A. and Slomiany B.L. (2003) Lipidomic processes in homeostatic and LPS- modified cell renewal cycle. Role of phosphatidylinositol 3-kinase pathway in biomembrane synthesis and restitution of apical epithelial membrane. Journal of Physiology and Pharmacology, 54, 533-551.
[30] Visnjic, D. and Banfic, H. (2007) Nuclear phospholipid signaling : Phosphatidylinositol-specific phospholipase C and phosphoinositide 3-kinase. Pflugers Archives, 455, 19-30. doi:10.1007/s00424-007-0288-1
[31] Sekine, T. and Raben, D.M. (2004) Nuclear production and metabolism of diacylglycerol. European Journal of Histochemistry, 48, 77-82.
[32] Alcazar-Roman, A.R. and Wente, S.R. (2008) Inositol polyphosphates: a new frontier for regulating gene expression. Chromosoma, 117, 1-13. doi:10.1007/s00412-007-0126-4
[33] Brown, D.A. (2006) Lipid rafts, detergent-resistant membranes and raft targeting signals. Physiology, 21, 430-439. doi:10.1152/physiol.00032.2006
[34] Snoek, G.T. (2004) Phosphatidylinositol transfer protein: emerging roles in cell proliferation, cell death and survival. IUBMB Life, 56, 467-475. doi:10.1080/15216540400012152
[35] Yokogawa, T., Nagata, S., Nishio, Y., Tsutsumi, T., Ihara, S., Shirai, R., Morita, K., Umeda, M., Shirai, Y., Saitoh, N. and Fukui, Y. (2000) Evidence that 3’- phosphorylated polyphosphoinositides are generated at the nuclear surface: use immunostaining technique with specific monoclonal antibodies specific for PI3,4P2. FEBS Letters, 473, 222-226. doi:10.1016/S0014-5793(00)01535-0
[36] Fagone, P. and Jackowski, S. (2009) Membrane phospholipid synthesis and endoplasmic reticulum function. Journal of Lipid Research, 50, S311-S316. doi:10.1194/jlr.R800049-JLR200
[37] Theerthagiri, G., Eisenhardt, N., Schwarz, H. and Antoninin, W. (2010) The nucleoporin Nup188 controls passage of membrane proteins across the nuclear pore complex. Journal of Cell Biology, 189, 1129-1142. doi:10.1083/jcb.200912045

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