Home LiteratureArticle Details
PMID: 17095657 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

PI(3,4,5)P3 and PI(4,5)P2 lipids target proteins with polybasic clusters to the plasma membrane.

Science (New York, N.Y.) ·Vol. 314 ·No. 5804 ·2006-12-01 ·Pages 1458-61

Heo WD, Inoue T, Park WS, Kim ML, Park BO, Wandless TJ, Meyer T

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.

MeSH Terms
ADP-Ribosylation Factors/chemistry,metabolism Amino Acid Motifs Amino Acid Sequence Animals Cell Membrane/metabolism GTP Phosphohydrolases/chemistry,metabolism HeLa Cells Humans Hydrophobic and Hydrophilic Interactions Kinetics Mice Molecular Sequence Data NIH 3T3 Cells Phosphatidylinositol 4,5-Diphosphate/metabolism Phosphatidylinositol Phosphates/metabolism Second Messenger Systems Signal Transduction Static Electricity rab GTP-Binding Proteins/chemistry,metabolism ras Proteins/chemistry,metabolism rho GTP-Binding Proteins/metabolism
Chemicals
Phosphatidylinositol 4,5-Diphosphate Phosphatidylinositol Phosphates phosphatidylinositol 3,4,5-triphosphate GTP Phosphohydrolases ADP-Ribosylation Factors rab GTP-Binding Proteins ras Proteins rho GTP-Binding Proteins
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Heo Won Do
Department of Molecular Pharmacology, 318 Campus Drive, Clark Building, Stanford University Medical School, Stanford, CA 94305, USA.
Inoue Takanari
Park Wei Sun
Kim Man Lyang
Park Byung Ouk
Wandless Thomas J
Meyer Tobias
References (23)
23 references, click to expand
  1. Phosphatidylinositol 4,5-bisphosphate functions as a second messenger that regulates cytoskeleton-plasma membrane adhesion.
    Cell. 2000 Jan 21;100(2):221-8 PMID: 10660045
  2. Binding of prenylated and polybasic peptides to membranes: affinities and intervesicle exchange.
    Biochemistry. 1995 Sep 19;34(37):11910-8 PMID: 7547927
  3. Rapid chemically induced changes of PtdIns(4,5)P2 gate KCNQ ion channels.
    Science. 2006 Dec 1;314(5804):1454-7 PMID: 16990515
  4. Plasma membrane phosphoinositide organization by protein electrostatics.
    Nature. 2005 Dec 1;438(7068):605-11 PMID: 16319880
  5. LY294002 and LY303511 sensitize tumor cells to drug-induced apoptosis via intracellular hydrogen peroxide production independent of the phosphoinositide 3-kinase-Akt pathway.
    Cancer Res. 2005 Jul 15;65(14):6264-74 PMID: 16024628
  6. An inducible translocation strategy to rapidly activate and inhibit small GTPase signaling pathways.
    Nat Methods. 2005 Jun;2(6):415-8 PMID: 15908919
  7. An acylation cycle regulates localization and activity of palmitoylated Ras isoforms.
    Science. 2005 Mar 18;307(5716):1746-52 PMID: 15705808
  8. Endomembrane trafficking of ras: the CAAX motif targets proteins to the ER and Golgi.
    Cell. 1999 Jul 9;98(1):69-80 PMID: 10412982
  9. Receptor-induced transient reduction in plasma membrane PtdIns(4,5)P2 concentration monitored in living cells.
    Curr Biol. 1998 Mar 12;8(6):343-6 PMID: 9512420
  10. ADP-ribosylation factor 6 regulates a novel plasma membrane recycling pathway.
    J Cell Biol. 1997 Oct 6;139(1):49-61 PMID: 9314528
  11. Rin, a neuron-specific and calmodulin-binding small G-protein, and Rit define a novel subfamily of ras proteins.
    J Neurosci. 1996 Nov 1;16(21):6784-94 PMID: 8824319
  12. SRF-dependent gene expression is required for PI3-kinase-regulated cell proliferation.
    EMBO J. 2000 Sep 15;19(18):4955-66 PMID: 10990459
  13. N-terminally myristoylated Ras proteins require palmitoylation or a polybasic domain for plasma membrane localization.
    Mol Cell Biol. 1994 Jul;14(7):4722-30 PMID: 8007974
  14. Cloning of two novel ADP-ribosylation factor-like proteins and characterization of their differential expression in 3T3-L1 cells.
    J Biol Chem. 1994 Jun 3;269(22):15683-8 PMID: 8195219
  15. Interaction cloning of protein kinase C substrates.
    J Biol Chem. 1993 Apr 5;268(10):6858-61 PMID: 8463212
  16. Controlling the location and activation of Rab GTPases.
    Curr Opin Cell Biol. 2004 Aug;16(4):451-7 PMID: 15261679
  17. Cell biology. Integrins, rafts, Rac, and Rho.
    Science. 2004 Feb 6;303(5659):773-4 PMID: 14764856
  18. Specific localization and timing in neuronal signal transduction mediated by protein-lipid interactions.
    Neuron. 2003 Oct 9;40(2):319-30 PMID: 14556711
  19. Switch-of-function mutants based on morphology classification of Ras superfamily small GTPases.
    Cell. 2003 May 2;113(3):315-28 PMID: 12732140
  20. PIP(2) and proteins: interactions, organization, and information flow.
    Annu Rev Biophys Biomol Struct. 2002;31:151-75 PMID: 11988466
  21. The effector domain of myristoylated alanine-rich C kinase substrate binds strongly to phosphatidylinositol 4,5-bisphosphate.
    J Biol Chem. 2001 Feb 16;276(7):5012-9 PMID: 11053422
  22. Differential localization of Rho GTPases in live cells: regulation by hypervariable regions and RhoGDI binding.
    J Cell Biol. 2001 Jan 8;152(1):111-26 PMID: 11149925
  23. Translocation and reversible localization of signaling proteins: a dynamic future for signal transduction.
    Cell. 2000 Oct 13;103(2):181-4 PMID: 11057890
Article Info
Journal
Science (New York, N.Y.)
Abbr.
Science
ISSN
1095-9203
DOI
10.1126/science.1134389
Published
2006-12-01
Epub
2006-00-09
Pages
1458-61
Language
English
Region
United States
NLM ID
0404511
PMCID
PMC3579512
Subset
IM
Grants
NIMH NIH HHS · R01 MH064801 · United States
NIGMS NIH HHS · R01 GM063702 · United States
NIGMS NIH HHS · R01 GM030179-24A1 · United States
NIGMS NIH HHS · R01 GM030179 · United States
NIGMS NIH HHS · R01 GM030179-25 · United States
Corrections
CommentIn
PMID: 17095656
External Links
PubMed source DOI: 10.1126/science.1134389 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2