Flavaglines Stimulate Transient Receptor Potential Melastatin Type 6 (TRPM6) Channel Activity

PloS One
Maxime G BlanchardJoost G Hoenderop

Abstract

Magnesium (Mg2+) is essential for enzymatic activity, brain function and muscle contraction. Blood Mg2+ concentrations are tightly regulated between 0.7 and 1.1 mM by Mg2+ (re)absorption in kidney and intestine. The apical entry of Mg2+ in (re)absorbing epithelial cells is mediated by the transient receptor potential melastatin type 6 (TRPM6) ion channel. Here, flavaglines are described as a novel class of stimulatory compounds for TRPM6 activity. Flavaglines are a group of natural and synthetic compounds that target the ubiquitously expressed prohibitins and thereby affect cellular signaling. By whole-cell patch clamp analyses, it was demonstrated that nanomolar concentrations of flavaglines increases TRPM6 activity by ∼2 fold. The stimulatory effects were dependent on the presence of the alpha-kinase domain of TRPM6, but did not require its phosphotransferase activity. Interestingly, it was observed that two natural occurring TRPM6 mutants with impaired insulin-sensitivity, TRPM6-p.Val1393Ile and TRPM6-p.Lys1584Glu, are not sensitive to flavagline stimulation. In conclusion, we have identified flavaglines as potent activators of TRPM6 activity. Our results suggest that flavaglines stimulate TRPM6 via the insulin receptor sign...Continue Reading

References

May 29, 2002·Nature Genetics·Roxanne Y WalderVal C Sheffield
Mar 28, 2003·American Journal of Physiology. Cell Physiology·Alex W CohenMichael P Lisanti
Oct 25, 2003·The Journal of Biological Chemistry·Thomas VoetsJoost G J Hoenderop
Jul 20, 2004·Nature Cell Biology·Vassilios J BezzeridesDavid E Clapham
Sep 10, 2005·The Journal of Biological Chemistry·Carsten SchmitzAnne-Laure Perraud
Jun 16, 2007·Nephron. Experimental Nephrology·Tobias B HuberThomas Benzing
Sep 4, 2007·Trends in Cell Biology·Duncan T BrowmanStephen M Robbins
Feb 9, 2008·Current Biology : CB·Gang CaoJoost G J Hoenderop
May 21, 2008·The Journal of Biological Chemistry·Stéphanie ThébaultJoost G J Hoenderop
Sep 19, 2008·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Alvaro YogiRhian M Touyz
Dec 17, 2008·Journal of the American Society of Nephrology : JASN·Stéphanie ThebaultRené J Bindels
Oct 27, 2009·Biochemical and Biophysical Research Communications·Sudharsana R Ande, Suresh Mishra
Jun 30, 2010·The Journal of Biological Chemistry·Gang CaoJoost G J Hoenderop
Dec 15, 2010·Journal of Medicinal Chemistry·Frédéric ThuaudLaurent Désaubry
Nov 9, 2011·PloS One·Yohann BernardLaurent Désaubry
Jun 27, 2012·Proceedings of the National Academy of Sciences of the United States of America·Anil V NairJoost G Hoenderop
Jun 29, 2012·Journal of Cellular Physiology·Saori Morino-KogaHirofumi Kai
Mar 26, 2013·Chemistry & Biology·Frédéric ThuaudLaurent Désaubry
May 10, 2013·American Journal of Physiology. Cell Physiology·Marc AndersonStuart E Dryer
Oct 4, 2013·American Journal of Physiology. Renal Physiology·Jeroen H F de BaaijJoost G J Hoenderop
Nov 23, 2013·Future Medicinal Chemistry·Christine BasmadjianLaurent Désaubry
Dec 19, 2013·Journal of Cellular Physiology·Indrajit ChowdhuryKelwyn Thomas
Jan 5, 2014·The Journal of Biological Chemistry·Zheng ZhangAndrea Fleig
Mar 22, 2014·The Biochemical Journal·Jenny van der WijstDario R Alessi
May 3, 2014·Natural Product Reports·Li PanA Douglas Kinghorn
May 27, 2014·Cellular and Molecular Life Sciences : CMLS·Katherine BrandaoCarsten Schmitz
Feb 1, 2012·Clinical Kidney Journal·Jeroen H F de BaaijRené J M Bindels

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Citations

Jul 1, 2017·Arteriosclerosis, Thrombosis, and Vascular Biology·Anique D Ter BraakeJeroen H F de Baaij
Jul 8, 2015·Journal of the American Society of Nephrology : JASN·Maxime G BlanchardJoost G J Hoenderop
Jun 29, 2016·Scientific Reports·Jeroen H F de BaaijJoost G J Hoenderop
Nov 13, 2018·Pflügers Archiv : European journal of physiology·Francisco J ArjonaJeroen H F de Baaij
Jan 29, 2019·Experimental Cell Research·Katsuhiro UzawaHideki Tanzawa
Oct 10, 2020·Bioorganic & Medicinal Chemistry Letters·Dong WangLaurent Désaubry

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Methods Mentioned

BETA
pull down
transfection
phosphotransferase
PMA

Software Mentioned

Patchmaster

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