Ric-8A-mediated stabilization of the trimeric G protein subunit Gαi is inhibited by pertussis toxin-catalyzed ADP-ribosylation

Kanako Chishiki, Sachiko Kamakura, Junya Hayase, Satoru Yuzawa, Hideki Sumimoto

Research output: Contribution to journalArticlepeer-review


The heterotrimeric G protein subunit Gαi can be activated by G protein-coupled receptors and the cytosolic protein Ric-8A, the latter of which is also known to prevent ubiquitin-dependent degradation of Gαi. Here we show that the amounts of the three Gαi-related proteins Gαi1, Gαi2, and Gαi3, but not that of Gαq, are rapidly decreased by cell treatment with pertussis toxin (PTX). The decrease appears to be due to ADP-ribosylation of Gαi, because PTX treatment does not affect the amount of a mutant Gαi2 carrying alanine substitution for Cys352, the residue that is ADP-ribosylated by the toxin. The presence of endogenous and exogenous Ric-8A increases Gαi stability as shown in cells treated with the protein synthesis inhibitor cycloheximide; however, Ric-8A fails to efficiently stabilize ADP-ribosylated Gαi. The failure agrees with the inability of Ric-8A to bind to ADP-ribosylated Gαi both in vitro and in vivo. Thus PTX appears to exert its pathological effects at least in part by converting Gαi to an unstable ADP-ribosylated form, in addition to the well-known inability of ADP-ribosylated Gαi to transduce signals triggered by G protein-coupled receptors.

Original languageEnglish
Pages (from-to)941-945
Number of pages5
JournalBiochemical and Biophysical Research Communications
Issue number3
Publication statusPublished - Feb 12 2017

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology


Dive into the research topics of 'Ric-8A-mediated stabilization of the trimeric G protein subunit Gαi is inhibited by pertussis toxin-catalyzed ADP-ribosylation'. Together they form a unique fingerprint.

Cite this