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

Do Heo Won, Takanari Inoue, Sun Park Wei, Lyang Kim Man, Ouk Park Byung, Thomas J. Wandless, Tobias Meyer

Research output: Contribution to journalArticlepeer-review

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)P 2. 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.

Original languageEnglish (US)
Pages (from-to)1458-1461
Number of pages4
JournalScience
Volume314
Issue number5804
DOIs
StatePublished - Dec 1 2006
Externally publishedYes

ASJC Scopus subject areas

  • General

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