A FRET map of membrane anchors suggests distinct microdomains of heterotrimeric G proteins

Daniel Abankwa, H Vogel

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44 Citations (Scopus)


The standard model of heterotrimeric G protein signaling postulates a dissociation of G alpha and G beta gamma subunits after activation. We hypothesized that the different combination of lipid-modifications on G alpha and G alpha beta gamma subunits directs them into different microdomains. By characterizing rapidly and at high sensitivity 38 fluorescence resonance energy transfer (FRET) pairs of heterotrimeric-G-protein constructs, we defined their microdomains in relation to each other, free from the constraints of the raft/non-raft dualism. We estimated that in a cell similar to 30% of these membrane-anchored proteins are mostly clustered in 340016,200 copies of 30-nm microdomains. We found that the membrane anchors of G alpha and G alpha beta gamma subunits of both the G(i/o) and G(q) family co-cluster differently with microdomain markers. Moreover, anchors of the G alpha(i/o) and G alpha(q) subunits co-clustered only weakly, whereas constructs that contained the anchors of the corresponding heterotrimers co-clustered considerably, suggesting the existence of at least three types of microdomain. Finally, FRET experiments with full-length heterotrimeric G proteins confirmed that the inactive, heterotrimerized G alpha subunit is in microdomains shared by heterotrimers from different subclasses, from where it displaces upon activation into a membrane-anchor- and subclass-specific microdomain.
Original languageUndefined/Unknown
Pages (from-to)2953–2962
Number of pages10
JournalJournal of Cell Science
Issue number16
Publication statusPublished - 2007
MoE publication typeA1 Journal article-refereed


  • FRET
  • heterotrimeric G protein
  • microdomain
  • nanodomain
  • raft

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