Gαi -mediated TRPC4 activation by polycystin-1 contributes to endothelial function via STAT1 activation

Scientific Reports
Misun KwakInsuk So

Abstract

Hypertension and aneurysm are frequently associated with autosomal dominant polycystic kidney disease (ADPKD) caused by polycystin-1 (PC1) mutations, which is closely related to endothelial dysfunction. PC1 is an atypical G-protein-coupled receptor that activates G-proteins by self-cleavage; currently, however, the molecular and cellular mechanisms of the associated intracellular signaling and ion channel activation remain poorly elucidated. Here, we report an activation mechanism of a calcium-permeable canonical transient receptor potential 4 (TRPC4) channel by PC1 and its endothelial function. We found that the inhibitory Gαi3 protein selectively bound to the G-protein-binding domain on the C-terminus of PC1. The dissociation of Gαi3 upon cleavage of PC1 increased TRPC4 activity. Calcium influx through TRPC4 activated the transcription factor STAT1 to regulate cell proliferation and death. The down-regulation of PC1/TRPC4/STAT1 disrupted migration of endothelial cell monolayers, leading to an increase in endothelial permeability. These findings contribute to greater understanding of the high risk of aneurysm in patients with ADPKD.

References

Oct 30, 1998·Biochemical and Biophysical Research Communications·S C ParnellJ P Calvet
Apr 14, 1999·Kidney International·N S MurciaE D Avner
Oct 21, 1999·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·L MarianiR W Seiler
Mar 4, 2000·Proceedings of the National Academy of Sciences of the United States of America·K KimM A Arnaout
Jun 6, 2000·The Journal of Biological Chemistry·M SchaeferG Schultz
Oct 25, 2000·The Journal of Biological Chemistry·D H VandorpeS L Alper
Oct 11, 2001·Proceedings of the National Academy of Sciences of the United States of America·C BoulterR Sandford
Jan 12, 2002·The Journal of Biological Chemistry·Patrick DelmasJing Zhou
Mar 20, 2002·The Journal of Biological Chemistry·Linda J NewbyAlbert C M Ong
Sep 5, 2002·Nature Reviews. Molecular Cell Biology·David E Levy, J E Darnell
Dec 17, 2002·Proceedings of the National Academy of Sciences of the United States of America·Feng QianGregory G Germino
Apr 1, 2004·European Journal of Human Genetics : EJHG·Hyunho KimSeongman Kang
Apr 3, 2004·The Journal of Biological Chemistry·Victor BabichChou-Long Huang
Nov 17, 2004·The Journal of Clinical Investigation·Veronique ChauvetMichael J Caplan
Oct 29, 2005·Circulation Research·Xiaoqiang Yao, Christopher J Garland
Dec 2, 2005·Journal of the American Society of Nephrology : JASN·Tamio YamaguchiDarren P Wallace
Jan 7, 2006·Journal of the American Society of Nephrology : JASN·Bruna PelucchiOttorino Belluzzi
Feb 3, 2006·Journal of the American Society of Nephrology : JASN·Manila BocaAlessandra Boletta
Jan 24, 2007·Physiological Reviews·Bernd NiliusJohn A Peters
Apr 17, 2007·Lancet·Vicente E TorresYves Pirson
Feb 16, 2008·Current Opinion in Nephrology and Hypertension·Ryuji InoueAkira Honda
Apr 8, 2010·Clinical Science·Scott Earley, Joseph E Brayden
Dec 18, 2010·Stroke; a Journal of Cerebral Circulation·H W XuMing Hua Li
Feb 4, 2011·Advances in Experimental Medicine and Biology·Alexis Hofherr, Michael Köttgen
Mar 24, 2011·Cardiovascular Research·Carole JungMiguel A Valverde
Apr 27, 2011·Proceedings of the National Academy of Sciences of the United States of America·Jeffrey J TalbotThomas Weimbs
Jun 29, 2011·The Journal of Biological Chemistry·Kevin J PaavolaRandy A Hall
Jul 5, 2013·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·David MerrickMichael J Caplan
Oct 17, 2013·Stroke; a Journal of Cerebral Circulation·Nohra ChalouhiDavid Hasan
Jul 3, 2015·Brain : a Journal of Neurology·Chansik HongInsuk So

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Citations

Nov 22, 2018·Journal of Cellular Biochemistry·Antonios N GargalionisAthanasios G Papavassiliou
Jun 3, 2020·International Journal of Molecular Sciences·Tamara RosenbaumFrancisco Torres-Quiroz
Dec 23, 2020·International Journal of Molecular Sciences·Giulia GagnoAneta Aleksova
Apr 20, 2020·Cellular Signalling·Robin L Maser, James P Calvet
Mar 30, 2021·Clinical Kidney Journal·Steven Van Laecke, Wim Van Biesen
Jun 18, 2021·Journal of Endovascular Therapy : an Official Journal of the International Society of Endovascular Specialists·Barbara InfanteGiovanni Stallone

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Methods Mentioned

BETA
immunoprecipitation
FRET
co-immunoprecipitation
Co-IP
transfection
electrophoresis

Software Mentioned

MetaMorph
ImageJ
pClamp
Origin

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