Diversity of the Gβγ complexes defines spatial and temporal bias of GPCR signaling

Ikuo Masuho, Nickolas K. Skamangas, Brian S. Muntean, Kirill A. Martemyanov

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


The signal transduction by G-protein-coupled receptors (GPCRs) is mediated by heterotrimeric G proteins composed from one of the 16 Gα subunits and the inseparable Gβγ complex assembled from a repertoire of 5 Gβ and 12 Gγ subunits. However, the functional role of compositional diversity in Gβγ complexes has been elusive. Using optical biosensors, we examined the function of all Gβγ combinations in living cells and uncovered two major roles of Gβγ diversity. First, we demonstrate that the identity of Gβγ subunits greatly influences the kinetics and efficacy of GPCR responses at the plasma membrane. Second, we show that different Gβγ combinations are selectively dispatched from the plasma membrane to various cellular organelles on a timescale from milliseconds to minutes. We describe the mechanisms regulating these processes and document their implications for GPCR signaling via various Gα subunits, thereby illustrating a role for the compositional diversity of G protein heterotrimers.

Original languageEnglish (US)
Pages (from-to)324-337.e5
JournalCell Systems
Issue number4
StatePublished - Apr 21 2021
Externally publishedYes


  • BRET
  • G-protein-coupled receptor
  • GPCR
  • Gβγ
  • bioluminescence resonance energy transfer
  • cellular signaling
  • functional assays
  • heterotrimeric G proteins
  • organelles

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology
  • Cell Biology


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