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Science 314 (5804): 1458-1461

Copyright © 2006 by the American Association for the Advancement of Science

PI(3,4,5)P3 and PI(4,5)P2 Lipids Target Proteins with Polybasic Clusters to the Plasma Membrane

Won Do Heo,1 Takanari Inoue,1 Wei Sun Park,1 Man Lyang Kim,1 Byung Ouk Park,2 Thomas J. Wandless,1 Tobias Meyer1*

Abstract: Many signaling, cytoskeletal, and transport proteins have to be localized to the plasma membrane (PM) in order to carry out their function. We surveyed PM-targeting mechanisms by imaging the subcellular localization of 125 fluorescent protein–conjugated Ras, Rab, Arf, and Rho proteins. Out of 48 proteins that were PM-localized, 37 contained clusters of positively charged amino acids. To test whether these polybasic clusters bind negatively charged phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] lipids, we developed a chemical phosphatase activation method to deplete PM PI(4,5)P2. Unexpectedly, proteins with polybasic clusters dissociated from the PM only when both PI(4,5)P2 and phosphatidylinositol 3,4,5-trisphosphate [PI(3,4,5)P3] were depleted, arguing that both lipid second messengers jointly regulate PM targeting.

1 Department of Molecular Pharmacology, 318 Campus Drive, Clark Building, Stanford University Medical School, Stanford, CA 94305, USA.
2 Division of Applied Life Science (BK21 Program) and Environmental Biotechnology National Core Research Center, Gyeongsang National University, Jinju 660-701, Korea.

* To whom correspondence should be addressed. E-mail: tobias1{at}stanford.edu

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Regulation of Membrane Trafficking, Cytoskeleton Dynamics, and Cell Polarity by ROP/RAC GTPases.
S. Yalovsky, D. Bloch, N. Sorek, and B. Kost (2008)
Plant Physiology 147, 1527-1543
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Identification of Regions Required for Apical Membrane Localization of Human Multidrug Resistance Protein 2.
P. E. Bandler, C. J. Westlake, C. E. Grant, S. P. C. Cole, and R. G. Deeley (2008)
Mol. Pharmacol. 74, 9-19
   Abstract »    Full Text »    PDF »
Phospholipase D Activity Regulates Integrin-mediated Cell Spreading and Migration by Inducing GTP-Rac Translocation to the Plasma Membrane.
Y. C. Chae, J. H. Kim, K. L. Kim, H. W. Kim, H. Y. Lee, W. D. Heo, T. Meyer, P.-G. Suh, and S. H. Ryu (2008)
Mol. Biol. Cell 19, 3111-3123
   Abstract »    Full Text »    PDF »
Role for Myosin II in Regulating Positioning of Salmonella-Containing Vacuoles and Intracellular Replication.
J. A. Wasylnka, M. A. Bakowski, J. Szeto, M. B. Ohlson, W. S. Trimble, S. I. Miller, and J. H. Brumell (2008)
Infect. Immun. 76, 2722-2735
   Abstract »    Full Text »    PDF »
Dissecting the role of PtdIns(4,5)P2 in endocytosis and recycling of the transferrin receptor.
N. Abe, T. Inoue, T. Galvez, L. Klein, and T. Meyer (2008)
J. Cell Sci. 121, 1488-1494
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Dual Fatty Acyl Modification Determines the Localization and Plasma Membrane Targeting of CBL/CIPK Ca2+ Signaling Complexes in Arabidopsis.
O. Batistic, N. Sorek, S. Schultke, S. Yalovsky, and J. Kudla (2008)
PLANT CELL 20, 1346-1362
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Diffusion Coefficient of Fluorescent Phosphatidylinositol 4,5-bisphosphate in the Plasma Membrane of Cells.
U. Golebiewska, M. Nyako, W. Woturski, I. Zaitseva, and S. McLaughlin (2008)
Mol. Biol. Cell 19, 1663-1669
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A brain-specific SGK1 splice isoform regulates expression of ASIC1 in neurons.
M. F. Arteaga, T. Coric, C. Straub, and C. M. Canessa (2008)
PNAS 105, 4459-4464
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Interaction between the Human Immunodeficiency Virus Type 1 Gag Matrix Domain and Phosphatidylinositol-(4,5)-Bisphosphate Is Essential for Efficient Gag Membrane Binding.
V. Chukkapalli, I. B. Hogue, V. Boyko, W.-S. Hu, and A. Ono (2008)
J. Virol. 82, 2405-2417
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Membrane Phosphatidylserine Regulates Surface Charge and Protein Localization.
T. Yeung, G. E. Gilbert, J. Shi, J. Silvius, A. Kapus, and S. Grinstein (2008)
Science 319, 210-213
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Intestinal Ca2+ wave dynamics in freely moving C. elegans coordinate execution of a rhythmic motor program.
K. Nehrke, J. Denton, and W. Mowrey (2008)
Am J Physiol Cell Physiol 294, C333-C344
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EGF-induced PIP2 hydrolysis releases and activates cofilin locally in carcinoma cells.
J. van Rheenen, X. Song, W. van Roosmalen, M. Cammer, X. Chen, V. DesMarais, S.-C. Yip, J. M. Backer, R. J. Eddy, and J. S. Condeelis (2007)
J. Cell Biol. 179, 1247-1259
   Abstract »    Full Text »    PDF »

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