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

✍ Scribed by Heo, W. D.; Inoue, T.; Park, W. S.; Kim, M. L.; Park, B. O.; Wandless, T. J.; Meyer, T.

• Book ID: 118181636
• Publisher: American Association for the Advancement of Science
• Year: 2006
• Tongue: English
• Weight: 863 KB
• Volume: 314
• Category: Article
• ISSN: 0036-8075
• DOI: 10.1126/science.1134389

✦ Synopsis

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)P
~2~
] 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)P
~2~
and phosphatidylinositol 3,4,5-trisphosphate [PI(3,4,5)P
~3~
] were depleted, arguing that both lipid second messengers jointly regulate PM targeting.