Severe myopathy in mice lacking the MEF2/SRF-dependent gene leiomodin-3

The Journal of Clinical Investigation
Bercin K CenikNing Liu

Abstract

Maintenance of skeletal muscle structure and function requires a precise stoichiometry of sarcomeric proteins for proper assembly of the contractile apparatus. Absence of components of the sarcomeric thin filaments causes nemaline myopathy, a lethal congenital muscle disorder associated with aberrant myofiber structure and contractility. Previously, we reported that deficiency of the kelch-like family member 40 (KLHL40) in mice results in nemaline myopathy and destabilization of leiomodin-3 (LMOD3). LMOD3 belongs to a family of tropomodulin-related proteins that promote actin nucleation. Here, we show that deficiency of LMOD3 in mice causes nemaline myopathy. In skeletal muscle, transcription of Lmod3 was controlled by the transcription factors SRF and MEF2. Myocardin-related transcription factors (MRTFs), which function as SRF coactivators, serve as sensors of actin polymerization and are sequestered in the cytoplasm by actin monomers. Conversely, conditions that favor actin polymerization de-repress MRTFs and activate SRF-dependent genes. We demonstrated that the actin nucleator LMOD3, together with its stabilizing partner KLHL40, enhances MRTF-SRF activity. In turn, SRF cooperated with MEF2 to sustain the expression of LMOD3...Continue Reading

References

Feb 15, 2000·The Journal of Biological Chemistry·F J NayaE N Olson
Apr 25, 2001·Genomics·C A ConleyV M Fowler
May 3, 2001·American Journal of Human Genetics·B IlkovskiK N North
Mar 26, 2002·FEBS Letters·Eija PaunolaPekka Lappalainen
Apr 16, 2002·Science·Hai WuR Sanders Williams
Oct 25, 2002·Proceedings of the National Academy of Sciences of the United States of America·Da-Zhi WangEric N Olson
May 7, 2003·Cell·Francesc MirallesRichard Treisman
Mar 31, 2005·Molecular and Cellular Biology·Koichiro KuwaharaEric N Olson
Aug 25, 2006·American Journal of Physiology. Cell Physiology·Joseph M MianoKeigi Fujiwara
Apr 7, 2007·The Journal of Clinical Investigation·Koichiro KuwaharaEric N Olson
Oct 20, 2007·Annals of the New York Academy of Sciences·Marie-France CarlierEric Guittet
Oct 26, 2007·Development·Matthew J Potthoff, Eric N Olson
Apr 2, 2008·Molecular and Cellular Biology·Mi-Sung KimEric N Olson
Apr 12, 2008·Science·David ChereauRoberto Dominguez
May 2, 2009·Trends in Cell Biology·Britta Qualmann, Michael M Kessels
Mar 20, 2010·Nature Reviews. Molecular Cell Biology·Kenneth G Campellone, Matthew D Welch
Apr 24, 2010·Nature Reviews. Molecular Cell Biology·Eric N Olson, Alfred Nordheim
Aug 26, 2010·Journal of Cell Science·Takehiro TsukadaCarol C Gregorio
Dec 24, 2010·Nature Biotechnology·Jeffrey C MillerEdward J Rebar
Mar 19, 2011·Proceedings of the National Academy of Sciences of the United States of America·Aibin HeWilliam T Pu
Jul 9, 2011·The Journal of Clinical Investigation·Ning LiuEric N Olson
Jul 25, 2012·Acta Neuropathologica·Kristen J NowakNigel G Laing
Sep 25, 2012·Nature·Victoria M BedellStephen C Ekker
Apr 30, 2013·Handbook of Clinical Neurology·Norma Beatriz Romero, Nigel F Clarke
Jul 3, 2013·Proceedings of the National Academy of Sciences of the United States of America·Benjamin R NelsonEric N Olson
Jul 23, 2013·Nature·Douglas P MillayEric N Olson
Sep 3, 2013·Current Opinion in Neurology·Norma B RomeroNigel F Clarke
Nov 6, 2013·Scientific Reports·Tomoko KatoShuji Takada
Feb 25, 2014·Methods : a Companion to Methods in Enzymology·Young Hoon SungHan-Woong Lee
Mar 5, 2014·Proceedings of the National Academy of Sciences of the United States of America·Ning LiuEric N Olson
Jun 25, 2014·Skeletal Muscle·Vandana A Gupta, Alan H Beggs
Jun 25, 2014·The Journal of Clinical Investigation·Ankit GargEric N Olson
Aug 12, 2014·Skeletal Muscle·Minttu MarttilaKatarina Pelin
Sep 23, 2014·Journal of Molecular Biology·Amy S RassonMargot E Quinlan
Sep 25, 2014·The Journal of Clinical Investigation·Michaela YuenNigel F Clarke

❮ Previous
Next ❯

Citations

Oct 22, 2015·Proceedings of the National Academy of Sciences of the United States of America·Christopher T PappasCarol C Gregorio
Jan 25, 2016·Journal of Molecular Neuroscience : MN·Yan CaoQiang Ma
Nov 19, 2015·Orphanet Journal of Rare Diseases·Emily J ToddGianina Ravenscroft
Sep 16, 2015·Nature Communications·Malgorzata BoczkowskaRoberto Dominguez
Jun 9, 2016·Cell & Bioscience·Shuang LiLing V Sun
Sep 27, 2016·Scientific Reports·Jin Rong OwReshma Taneja
Oct 29, 2017·Proceedings of the National Academy of Sciences of the United States of America·Tongbin WuJu Chen
Jul 8, 2016·Development·Bercin K CenikRhonda Bassel-Duby
Jan 23, 2016·The Journal of Experimental Biology·Miensheng ChuChristopher T Pappas
Jan 14, 2018·Journal of Ultrasound in Medicine : Official Journal of the American Institute of Ultrasound in Medicine·Michal BerkenstadtAnnick Raas-Rothschild
Jul 1, 2018·Journal of Medical Genetics·Sarah Jane BeecroftGianina Ravenscroft
Aug 23, 2017·ELife·Andres Ramirez-MartinezEric N Olson
Mar 16, 2017·Proceedings of the National Academy of Sciences of the United States of America·Danny HalimJoseph M Miano
Apr 25, 2017·Journal of Neuromuscular Diseases·Josine M de Winter, Coen A C Ottenheijm
Jan 4, 2020·PloS One·Lei Mi-MiCarol C Gregorio
Sep 5, 2015·Oncotarget·Sarah Sandaradura, Kathryn N North
Aug 18, 2017·American Journal of Medical Genetics. Part a·Megan AbbottLindsay C Burrage
Jun 23, 2019·Journal of Muscle Research and Cell Motility·Caroline A SewryCarina Wallgren-Pettersson
Feb 6, 2020·Neuromuscular Disorders : NMD·Florent MarguetAnnie Laquerrière
Jun 4, 2015·Disease Models & Mechanisms·Lei TianTian Xu
Nov 3, 2016·Journal of Cell Science·Stephanie Wales TobinJohn C McDermott
Sep 28, 2020·Experimental Cell Research·Fei-Hu LinLing V Sun
Jul 18, 2021·The FEBS Journal·Dmitri TolkatchevAlla S Kostyukova
Aug 5, 2021·Journal of Cellular and Molecular Medicine·Ruhui SongYao Xu

❮ Previous
Next ❯

Methods Mentioned

BETA
PCR
cleavage assay
ChIP
transgenic
electron microscopy
genotyping
confocal microscopy
transfection
transfections

Software Mentioned

ImageJ
TAL Effector Nucleotide Targeter

Related Concepts

Related Feeds

CREs: Gene & Cell Therapy

Gene and cell therapy advances have shown promising outcomes for several diseases. The role of cis-regulatory elements (CREs) is crucial in the design of gene therapy vectors. Here is the latest research on CREs in gene and cell therapy.