Heterotrimeric G proteins demonstrate differential sensitivity to β-arrestin dependent desensitization

Giulio Innamorati, Flavia Giannone, Francesca Guzzi, Gian Enrico Rovati, Maria Rosa Accomazzo, Bice Chini, Elisabetta Bianchi, Maria Vittoria Schiaffino, Giuseppe Tridente, Marco Parenti

Research output: Contribution to journalArticlepeer-review


G15 is a heterotrimeric G protein of the Gq/11 family. In this study, we describe its exceptional poor sensitivity to the general regulatory mechanism of G protein-coupled receptor (GPCR) desensitization. Enhancing β2 adrenergic receptor desensitization by arrestin overexpression, did not affect signalling to G15. Similarly, increased levels of arrestin did not affect G15 signalling triggered by the activation of V2 vasopressin and δ opioid receptors. Furthermore, co-immunoprecipitation experiments showed that G15 α subunit (as opposed to Gαq and Gαs) is recruited to a V2 vasopressin receptor mutant that is constitutively desensitized by β-arrestin. Interestingly, co-expression of Gα15 partially rescued cell surface localization and signalling capabilities of the same mutant receptor and reduced β2 adrenergic receptor internalization. Taken together, these findings provide evidence for a novel mechanism whereby GPCR desensitization can be bypassed and G15 can support sustained signalling in cells chronically exposed to hormones or neurotransmitters.

Original languageEnglish
Pages (from-to)1135-1142
Number of pages8
JournalCellular Signalling
Issue number7
Publication statusPublished - Jul 2009


  • Arrestin
  • Desensitization
  • G protein-coupled receptor
  • G15
  • GRK

ASJC Scopus subject areas

  • Cell Biology


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