G protein subunit dissociation and translocation regulate cellular response to receptor stimulation

PLoS One. 2009 Nov 11;4(11):e7797. doi: 10.1371/journal.pone.0007797.

Abstract

We examined the role of G proteins in modulating the response of living cells to receptor activation. The response of an effector, phospholipase C-beta to M3 muscarinic receptor activation was measured using sensors that detect the generation of inositol triphosphate or diacylglycerol. The recently discovered translocation of G betagamma from plasma membrane to endomembranes on receptor activation attenuated this response. A FRET based G protein sensor suggested that in contrast to translocating G betagamma, non-translocating G betagamma subunits do not dissociate from the alpha q subunit on receptor activation leading to prolonged retention of the heterotrimer state and an accentuated response. M3 receptors with tethered alpha q induced differential responses to receptor activation in cells with or without an endogenous translocation capable gamma subunit. G protein heterotrimer dissociation and betagamma translocation are thus unanticipated modulators of the intensity of a cell's response to an extracellular signal.

Publication types

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

MeSH terms

  • Animals
  • CHO Cells
  • Cell Membrane / metabolism
  • Cricetinae
  • Cricetulus
  • Dimerization
  • Fluorescence Resonance Energy Transfer
  • GTP-Binding Proteins / chemistry*
  • GTP-Binding Proteins / metabolism
  • Gene Expression Regulation*
  • Models, Biological
  • Phospholipase C beta / metabolism
  • Protein Structure, Tertiary
  • Protein Transport
  • Receptor, Muscarinic M3 / metabolism

Substances

  • Receptor, Muscarinic M3
  • Phospholipase C beta
  • GTP-Binding Proteins