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

Overview

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.

publication date

  • November 9, 2006

Research

keywords

  • Cell Membrane
  • GTP Phosphohydrolases
  • Phosphatidylinositol 4,5-Diphosphate
  • Phosphatidylinositol Phosphates

Identity

PubMed Central ID

  • PMC3579512

Scopus Document Identifier

  • 33845313646

Digital Object Identifier (DOI)

  • 10.1126/science.1131163

PubMed ID

  • 17095657

Additional Document Info

volume

  • 314

issue

  • 5804