Shuttling of G protein subunits between the plasma membrane and intracellular membranes

J Biol Chem. 2007 Aug 17;282(33):24092-8. doi: 10.1074/jbc.M704246200. Epub 2007 Jun 18.

Abstract

Heterotrimeric G proteins (alphabetagamma) mediate the majority of signaling pathways in mammalian cells. It is long held that G protein function is localized to the plasma membrane. Here we examined the spatiotemporal dynamics of G protein localization using fluorescence recovery after photobleaching, fluorescence loss in photobleaching, and a photoswitchable fluorescent protein, Dronpa. Unexpectedly, G protein subunits shuttle rapidly (t1/2 < 1 min) between the plasma membrane and intracellular membranes. We show that consistent with such shuttling, G proteins constitutively reside in endomembranes. Furthermore, we show that shuttling is inhibited by 2-bromopalmitate. Thus, contrary to present thought, G proteins do not reside permanently on the plasma membrane but are constantly testing the cytoplasmic surfaces of the plasma membrane and endomembranes to maintain G protein pools in intracellular membranes to establish direct communication between receptors and endomembranes.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Membrane / metabolism*
  • Fluorescence Recovery After Photobleaching
  • GTP-Binding Proteins / metabolism*
  • Humans
  • Intracellular Membranes / metabolism*
  • Kinetics
  • Palmitates / pharmacology
  • Protein Subunits / metabolism
  • Protein Transport

Substances

  • Palmitates
  • Protein Subunits
  • 2-bromopalmitate
  • GTP-Binding Proteins