Disease causing mutations in inverted formin 2 regulate its binding to G-actin, F-actin capping protein (CapZ α-1) and profilin 2.

Bioscience Reports
Ruth RollasonGavin I Welsh

Abstract

Focal segmental glomerulosclerosis (FSGS) is a devastating form of nephrotic syndrome which ultimately leads to end stage renal failure (ESRF). Mutations in inverted formin 2 (INF2), a member of the formin family of actin-regulating proteins, have recently been associated with a familial cause of nephrotic syndrome characterized by FSGS. INF2 is a unique formin that can both polymerize and depolymerize actin filaments. How mutations in INF2 lead to disease is unknown. In the present study, we show that three mutations associated with FSGS, E184K, S186P and R218Q, reduce INF2 auto-inhibition and increase association with monomeric actin. Furthermore using a combination of GFP-INF2 expression in human podocytes and GFP-Trap purification coupled with MS we demonstrate that INF2 interacts with profilin 2 and the F-actin capping protein, CapZ α-1. These interactions are increased by the presence of the disease causing mutations. Since both these proteins are involved in the dynamic turnover and restructuring of the actin cytoskeleton these changes strengthen the evidence that aberrant regulation of actin dynamics underlies the pathogenesis of disease.

References

Feb 19, 2000·Current Opinion in Cell Biology·B L GoodeG Barnes
Aug 3, 2001·Nature Cell Biology·A F PalazzoG G Gundersen
Feb 22, 2002·Journal of the American Society of Nephrology : JASN·Moin A SaleemPeter Mundel
Mar 4, 2005·Molecular Biology of the Cell·David R KovarThomas D Pollard
Jan 28, 2006·Cell·David R KovarThomas D Pollard
Feb 14, 2006·Methods in Enzymology·Elizabeth S Harris, Henry N Higgs
Oct 22, 2008·The Journal of Cell Biology·Laura Trinkle-MulcahyAngus Lamond
Apr 16, 2009·Journal of Cell Science·Ekta Seth ChhabraHenry N Higgs
May 22, 2009·Cell Motility and the Cytoskeleton·Aditya S Paul, Thomas D Pollard
Jul 28, 2009·Biochimica Et Biophysica Acta·F Bartolini, G G Gundersen
Nov 20, 2009·Kidney International·Peter Mundel, Jochen Reiser
Dec 10, 2009·Nature Reviews. Molecular Cell Biology·Melissa A ChesaroneBruce L Goode
Dec 22, 2009·Nature Genetics·Elizabeth J BrownMartin R Pollak
Apr 21, 2010·The Journal of Biological Chemistry·Trynette J van DuijnPeter L Hordijk
Jan 25, 2011·Journal of the American Society of Nephrology : JASN·Olivia BoyerCorinne Antignac
Oct 26, 2011·Nature Reviews. Nephrology·Gavin I Welsh, Moin A Saleem
Dec 23, 2011·The New England Journal of Medicine·Olivia BoyerGéraldine Mollet
Feb 16, 2012·Nephrology, Dialysis, Transplantation : Official Publication of the European Dialysis and Transplant Association - European Renal Association·Ilse M RoodJack F M Wetzels
Feb 24, 2012·Current Opinion in Nephrology and Hypertension·Vivette D D'Agati
Apr 12, 2012·The Journal of Cell Biology·Florian SteinbergPeter J Cullen
Aug 25, 2012·Molecular Biology of the Cell·Francesca BartoliniGregg G Gundersen
Mar 22, 2013·Kidney International·Beata S LipskaUNKNOWN PodoNet Consortium
Apr 27, 2013·Journal of the American Society of Nephrology : JASN·Hua SunMartin R Pollak
Aug 8, 2013·The Journal of Biological Chemistry·Vinay RamabhadranHenry N Higgs
Mar 7, 2014·Kidney International·Elizabeth J BrownMoumita Barua
Sep 11, 2014·Nature Reviews. Molecular Cell Biology·Marc EdwardsJohn A Cooper
Dec 30, 2014·Developmental Cell·Cristian SuarezDavid R Kovar
May 6, 2015·Proceedings of the National Academy of Sciences of the United States of America·Xiaowei ShaoG V Shivashankar
Jul 1, 2015·The Journal of Biological Chemistry·Pinar S GurelHenry N Higgs

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Citations

Sep 19, 2017·Cytoskeleton·Anna HegstedDavid Pruyne
Mar 4, 2018·Scientific Reports·Kathryn L GarnerRichard J M Coward
Sep 3, 2017·Journal of the American Society of Nephrology : JASN·Christoph Schell, Tobias B Huber
Aug 17, 2019·Journal of the American Society of Nephrology : JASN·Louise K FarmerGavin I Welsh
May 24, 2020·Journal of the American Society of Nephrology : JASN·Samet BayraktarRoland Wedlich-Söldner
May 27, 2020·Cellular and Molecular Life Sciences : CMLS·Leticia Labat-de-Hoz, Miguel A Alonso
Nov 15, 2020·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Sanja Sever
Apr 4, 2021·Biology·Govinda SharmaTimothy E Shutt

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Methods Mentioned

BETA
GTPases
PCR
co-immunoprecipitation
co-IP
transfection
pulldown
pull downs
pull down
pulled
co-IPs

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