Phosphate Number and Acyl Chain Length Determine the Subcellular Location and Lateral Mobility of Phosphoinositides

  • Cho, Hana (Department of Physiology, Kangwon National University School of Medicine) ;
  • Kim, Yeon A (National Research Laboratory for Cell Physiology and Department of Physiology, Seoul National University College of Medicine) ;
  • Ho, Won-Kyung (National Research Laboratory for Cell Physiology and Department of Physiology, Seoul National University College of Medicine)
  • Received : 2006.05.23
  • Accepted : 2006.06.25
  • Published : 2006.08.31

Abstract

Phosphoinositides are critical regulators of ion channel and transporter activity. There are multiple isomers of biologically active phosphoinositides in the plasma membrane and the different lipid species are non-randomly distributed. However, the mechanism by which cells impose selectivity and directionality on lipid movements and so generate a non-random lipid distribution remains unclear. In the present study we investigated which structural elements of phosphoinositides are responsible for their subcellular location and movement. We incubated phosphatidylinositol (PI), phosphatidylinositol 4-monophosphate (PI(4)P) and phosphatidylinositol 4,5-bisphosphate ($PI(4,5)P_2$) with short or long acyl chains in CHO and HEK cells. We show that phosphate number and acyl chain length determine cellular location and translocation movement. In CHO cells, $PI(4,5)P_2$ with a long acyl chain was released into the cytosol easily because of a low partition coefficient whereas long chain PI was released more slowly because of a high partition coefficient. In HEK cells, the cellular location and translocation movement of PI were similar to those of PI in CHO cells, whereas those of $PI(4,5)P_2$ were different; some mechanism restricted the translocation movement of $PI(4,5)P_2$, and this is in good agreement with the extremely low lateral diffusion of $PI(4,5)P_2$. In contrast to the dependence on the number of phosphates of the phospholipid head group of long acyl chain analogs, short acyl chain phospholipids easily undergo translocation movement regardless of cell type and number of phosphates in the lipid headgroup.

Keywords

Acknowledgement

Supported by : Korea Research Foundation

References

  1. Baukrowitz, T., Schulte, U., Oliver, D., Herlitze, S., Krauter, T., et al. (1998) PIP2 and PIP as determinants for ATP inhibition of KATP channels. Science 282, 1141−1144 https://doi.org/10.1126/science.282.5391.1141
  2. Chatelut, M., Leruth, M., Harzer, K., Dagan, A., Marchesini, S., et al. (1998) Natural ceramide is unable to escape the lysosome, in contrast to a fluorescent analogue. FEBS Lett. 426, 102−106
  3. Chattopadhyay, A. (1990) Chemistry and biology of N-(7- nitrobenz-2-oxa-1,3-diazol-4-yl)-labeled lipids: fluorescent probes of biological and model membranes. Chem. Phys. Lipids 53, 1−15 https://doi.org/10.1016/0009-3084(90)90128-E
  4. Cho, H., Lee, D., Lee, S. H., and Ho, W. K. (2005a) Receptorinduced depletion of phosphatidylinositol 4,5-bisphosphate inhibits inwardly rectifying K+ channels in a receptorspecific manner. Proc. Natl. Acad. Sci. USA 102, 4643−4648
  5. Cho, H., Kim, Y. A., Yoon, J. Y., Lee, D., Kim, J. H., et al. (2005b) Low mobility of phosphatidylinositol 4,5-bisphosphate underlies receptor specificity of Gq-mediated ion channel regulation in atrial myocytes. Proc. Natl. Acad. Sci. USA 102, 15241−15246
  6. Delmas, P., Coste, B., Gamper, N., and Shapiro, M. S. (2005) Phosphoinositide lipid second messengers: new paradigms for calcium channel modulation. Neuron 47, 179−182 https://doi.org/10.1016/j.neuron.2005.07.001
  7. Dewald, D. B., Ozaki, S., Malaviya, S., Shope, J. C., Manabe, K., et al. (2005) Cellular calcium mobilization in response to phosphoinositide delivery. Cell Calcium 38, 59−72 https://doi.org/10.1016/j.ceca.2005.06.004
  8. Fan, Z. and Makielski, J. C. (1997) Anionic phospholipids activate ATP-sensitive potassium channels. J. Biol. Chem. 272, 5388−5395
  9. Fan, Z., Gao, L., and Wang, W. (2003) Phosphatidic acid stimulates cardiac KATP channels like phosphatidylinositols, but with novel gating kinetics. Am. J. Physiol. Cell Physiol. 284, C94−102 https://doi.org/10.1152/ajpcell.00255.2002
  10. Fruman, D. A., Meyers, R. E., and Cantley, L. C. (1998) Phosphoinositide kinases. Annu. Rev. Biochem. 67, 481−507
  11. Hilgemann, D. W., Feng, S., and Nasuhoglu, C. (2001) The complex and intriguing lives of PIP2 with ion channels and transporters. Sci. STKE 2001, RE19
  12. Ho, I. H. and Murrell-Lagnado, R. D. (1999) Molecular mechanism for sodium-dependent activation of G protein-gated $K^+$ channels. J. Physiol. 520, 645−651 https://doi.org/10.1111/j.1469-7793.1999.00645.x
  13. Holthuis, J. C. and Levine, T. P. (2005) Lipid traffic: floppy drives and a superhighway. Nat. Rev. Mol. Cell. Biol. 6, 209− 220 https://doi.org/10.1038/nrm1591
  14. Krauter, T., Ruppersberg, J. P., and Baukrowitz, T. (2001) Phospholipids as modulators of K(ATP) channels: distinct mechanisms for control of sensitivity to sulphonylureas, K(+) channel openers, and ATP. Mol. Pharmacol. 59, 1086−1093
  15. Lopes, C. M., Zhang, H., Rohacs, T., Jin, T., Yang, J., et al. (2002) Alterations in conserved Kir channel-PIP2 interactions underlie channelopathies. Neuron 34, 933−944 https://doi.org/10.1016/S0896-6273(02)00725-0
  16. Ozaki, S., DeWald, D. B., Shope, J. C., Chen, J., and Prestwich, G. D. (2000) Intracellular delivery of phosphoinositides and inositol phosphates using polyamine carriers. Proc. Natl. Acad. Sci. USA 97, 11286−11291
  17. Rohacs, T., Chen, J., Prestwich, G. D., and Logothetis, D. E. (1999) Distinct specificities of inwardly rectifying K(+) channels for phosphoinositides. J. Biol. Chem. 274, 36065-36072. https://doi.org/10.1074/jbc.274.51.36065
  18. Shyng, S. L. and Nichols, C. G. (1998) Membrane phospholipid control of nucleotide sensitivity of KATP channels. Science 282, 1138−1141 https://doi.org/10.1126/science.282.5391.1141
  19. Stauffer, T. P., Ahn, S., and Meyer, T. (1998) Receptor-induced transient reduction in plasma membrane PtdIns(4,5)P2 concentration monitored in living cells. Curr. Biol. 8, 343−346 https://doi.org/10.1016/S0960-9822(98)70135-6
  20. Tian, W., Laffafian, I., Dewitt, S., and Hallett, M. B. (2003) Exclusion of exogenous phosphatidylinositol-3,4,5-trisphosphate from neutrophil-polarizing pseudopodia: stabilization of the uropod and cell polarity. EMBO Rep. 4, 982−988 https://doi.org/10.1038/sj.embor.embor947
  21. Tuominen, E. K., Holopainen, J. M., Chen, J., Prestwich, G. D., Bachiller, P. R., et al. (1999) Fluorescent phosphoinositide derivatives reveal specific binding of gelsolin and other actin regulatory proteins to mixed lipid bilayers. Eur. J. Biochem. 263, 85−92
  22. Venkataraman, K. and Futerman, A. (2000) Ceramide as a second messenger: sticky solutions to sticky problems. Trends Cell Biol. 10, 408−412
  23. Zhang, H., Craciun, L. C., Mirshahi, T., Rohacs, T., Lopes, C. M., et al. (2003) PIP(2) activates KCNQ channels, and its hydrolysis underlies receptor-mediated inhibition of M currents. Neuron 37, 963−975 https://doi.org/10.1016/S0896-6273(03)00125-9