PIP3 inhibition of RGS protein and its reversal by Ca2+/calmodulin mediate voltage-dependent control of the G protein cycle in a cardiac K+ channel

Proceedings of the National Academy of Sciences of the United States of America
Masaru IshiiY Kurachi

Abstract

Regulators of G protein signaling (RGS) accelerate intrinsic GTP hydrolysis on alpha subunits of trimeric G proteins and play crucial roles in the physiological regulation of G protein-mediated cell signaling. The control mechanisms of the action of RGS proteins per se are poorly clarified, however. We recently showed a physiological mode of action of a RGS protein in cardiac myocytes. The voltage-dependent formation of Ca2+/calmodulin facilitated the GTPase activity of RGS by an unidentified mechanism, which underlay the "relaxation" behavior of G protein-gated K+ (K(G)) channels. Here we report the mechanism which is the reversal by Ca2+/calmodulin of phosphatidylinositol-3,4,5,-trisphosphate (PIP3)-mediated inhibition of RGS. Purified RGS4 protein alone inhibited GTP-induced K(G) channel activity in inside-out patches from atrial myocytes. The inhibitory effect of RGS4 was reduced by PIP3 and restored by addition of Ca2+/calmodulin. The intracellular application of anti-PIP3 antibody abolished the RGS-dependent relaxation behavior of K(G) current in atrial myocytes. This study, therefore, reveals a general physiological control mechanism of RGS proteins by lipid-protein interaction.

References

Nov 30, 1978·Pflügers Archiv : European journal of physiology·A Noma, W Trautwein
Jan 1, 1987·Annual Review of Biochemistry·A G Gilman
Aug 1, 1981·Pflügers Archiv : European journal of physiology·O P HamillF J Sigworth
Dec 5, 1995·Proceedings of the National Academy of Sciences of the United States of America·L De VriesM G Farquhar
Sep 18, 1997·Proceedings of the National Academy of Sciences of the United States of America·C A DoupnikP Kofuji
Dec 31, 1997·The Journal of Clinical Investigation·T Michel, O Feron
Jan 27, 1998·The Journal of Biological Chemistry·S P SrinivasaK J Blumer
Mar 14, 1998·Proceedings of the National Academy of Sciences of the United States of America·J L SuiD E Logothetis
Feb 12, 1998·Neuron·W HeT G Wensel
Mar 20, 1999·The Journal of Biological Chemistry·I H Ho, R D Murrell-Lagnado
May 4, 1999·Trends in Cell Biology·L De Vries, M Gist Farquhar
Apr 21, 1999·Current Opinion in Cell Biology·S J LeeversM D Waterfield
May 5, 1999·The Journal of Physiology·D Kim, H Bang
Aug 27, 1999·Trends in Pharmacological Sciences·J R Hepler
May 29, 2001·Molecular Pathology : MP·B Valentinis, R Baserga

❮ Previous
Next ❯

Citations

Jan 8, 2005·The Journal of Membrane Biology·A B ZhainazarovB W Ache
Apr 5, 2005·Pflügers Archiv : European journal of physiology·Manpreet MutnejaPaul A Slesinger
Nov 11, 2003·Life Sciences·Masaru Ishii, Yoshihisa Kurachi
Jun 26, 2002·The Journal of Biological Chemistry·Danielle L IppolitoCharles Chavkin
May 19, 2010·Philosophical Transactions. Series A, Mathematical, Physical, and Engineering Sciences·Shingo MurakamiYoshihisa Kurachi
May 29, 2003·Proceedings of the National Academy of Sciences of the United States of America·Patrizia TosettiKathleen Dunlap
Oct 13, 2006·Proceedings of the National Academy of Sciences of the United States of America·James D BradyR Lane Brown
Mar 5, 2005·Cellular and Molecular Life Sciences : CMLS·C R McCuddenF S Willard
Mar 11, 2015·Journal of Molecular and Cellular Cardiology·Pooja S KrishnaswamyRobert A Rose
Aug 26, 2009·Journal of Molecular and Cellular Cardiology·Justus M B Anumonwo, Anatoli N Lopatin
Nov 17, 2007·Pharmacology & Therapeutics·Geetanjali BansalZhihui Xie
Oct 18, 2006·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Shuying Yang, Yi-Ping Li
Jul 11, 2012·Journal of Neuroendocrinology·P MelamedL Pnueli
Oct 13, 2006·Cell Calcium·Kirill KiselyovShmuel Muallem
May 12, 2006·Seminars in Cell & Developmental Biology·Gary B Willars
Oct 26, 2005·Biochemical and Biophysical Research Communications·Masaru IshiiYoshihisa Kurachi
Apr 16, 2008·European Journal of Pharmacology·Mariëlle C Hendriks-BalkAstrid E Alewijnse
Oct 26, 2005·Current Biology : CB·Thomas M Wilkie, Lisa Kinch
Sep 13, 2008·Current Biology : CB·Elliott M Ross
Sep 21, 2013·Biophysical Journal·Shingo MurakamiYoshihisa Kurachi
Nov 23, 2006·Biochemical Pharmacology·Jennifer S McCullarTheresa M Filtz
Aug 19, 2003·The Journal of Physiology·Yoshihisa Kurachi, Masaru Ishii
Jan 15, 2004·The Journal of Biological Chemistry·Matthieu RoussetPierre Charnet
Mar 5, 2005·Circulation Research·Evan L RiddlePaul A Insel
Jun 20, 2007·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Kaori IwaiMasaru Ishii
Aug 8, 2007·The Journal of Biological Chemistry·Patrick Osei-OwusuKendall J Blumer
Mar 20, 2009·American Journal of Physiology. Cell Physiology·Yuichiro MatsushitaYuji Imaizumi
Jan 21, 2010·Physiological Reviews·Hiroshi HibinoYoshihisa Kurachi
Feb 11, 2020·PLoS Computational Biology·Daniel MajoralRaul Vicente
Oct 6, 2005·Nihon yakurigaku zasshi. Folia pharmacologica Japonica·Masaru Ishii, Yoshihisa Kurachi
Nov 1, 2008·Expert Review of Clinical Pharmacology·Donard S DwyerEric J Aamodt
Apr 10, 2003·The Journal of Biological Chemistry·Yair Ben-ChaimHanna Parnas
Jun 13, 2009·Journal of Receptor and Signal Transduction Research·Yong ZhangTheresa M Filtz

❮ Previous
Next ❯

Related Concepts

Related Feeds

Arrhythmia

Arrhythmias are abnormalities in heart rhythms, which can be either too fast or too slow. They can result from abnormalities of the initiation of an impulse or impulse conduction or a combination of both. Here is the latest research on arrhythmias.

Atrial Filbrillation

Atrial fibrillation refers to the abnormal heart rhythm characterized by rapid and irregular beating of the atria. Here is the latest research.

Atrial Fibrillation

Atrial fibrillation is a common arrhythmia that is associated with substantial morbidity and mortality, particularly due to stroke and thromboembolism. Here is the latest research.

Calcium & Bioenergetics

Bioenergetic processes, including cellular respiration and photosynthesis, concern the transformation of energy by cells. Here is the latest research on the role of calcium in bioenergetics.