Survival motor neuron deficiency slows myoblast fusion through reduced myomaker and myomixer expression.

Journal of Cachexia, Sarcopenia and Muscle
Nikki M McCormackBarrington G Burnett

Abstract

Spinal muscular atrophy is an inherited neurodegenerative disease caused by insufficient levels of the survival motor neuron (SMN) protein. Recently approved treatments aimed at increasing SMN protein levels have dramatically improved patient survival and have altered the disease landscape. While restoring SMN levels slows motor neuron loss, many patients continue to have smaller muscles and do not achieve normal motor milestones. While timing of treatment is important, it remains unclear why SMN restoration is insufficient to fully restore muscle size and function. We and others have shown that SMN-deficient muscle precursor cells fail to efficiently fuse into myotubes. However, the role of SMN in myoblast fusion is not known. In this study, we show that SMN-deficient myoblasts readily fuse with wild-type myoblasts, demonstrating fusion competency. Conditioned media from wild type differentiating myoblasts do not rescue the fusion deficit of SMN-deficient cells, suggesting that compromised fusion may primarily be a result of altered membrane dynamics at the cell surface. Transcriptome profiling of skeletal muscle from SMN-deficient mice revealed altered expression of cell surface fusion molecules. Finally, using cell and mouse...Continue Reading

References

Oct 1, 1991·Journal of Child Neurology·E L ZalneraitisN Peress
Aug 1, 1997·Human Molecular Genetics·D D CoovertA H Burghes
May 26, 1999·Proceedings of the National Academy of Sciences of the United States of America·C L LorsonB Wirth
Aug 24, 2004·Laboratory Investigation; a Journal of Technical Methods and Pathology·Anne-Sophie ArnoldJean-Pierre Gies
Mar 14, 2007·The Journal of Cell Biology·T K RajendraA Gregory Matera
Jun 15, 2007·Neurobiology of Disease·Matthew E R ButchbachArthur H M Burghes
Mar 29, 2008·American Journal of Human Genetics·Yimin HuaAdrian R Krainer
Jan 23, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Lingling KongCharlotte J Sumner
Jul 9, 2009·Nature Reviews. Neuroscience·Arthur H M Burghes, Christine E Beattie
Aug 16, 2011·Human Molecular Genetics·Chantal A MutsaersThomas H Gillingwater
Jun 23, 2012·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Tara L MartinezCharlotte J Sumner
Jul 17, 2012·Human Molecular Genetics·Katherine V BriccenoBarrington G Burnett
Jul 20, 2012·Comparative and Functional Genomics·Herve Faralli, F Jeffrey Dilworth
Apr 25, 2013·Science Signaling·Sajedah M HindiAshok Kumar
Jul 23, 2013·Nature·Douglas P MillayEric N Olson
Apr 3, 2014·Human Molecular Genetics·Justin G BoyerRashmi Kothary
Aug 3, 2014·Genes & Development·Douglas P MillayEric N Olson
Feb 14, 2015·The Journal of Pharmacology and Experimental Therapeutics·Darren T HweeJeffrey R Jasper
Nov 6, 2015·International Journal of Molecular Sciences·Wen LuoXiquan Zhang
Jun 29, 2016·Scientific Reports·Marc-Olivier DeguiseRashmi Kothary
Jul 13, 2016·Molecular Therapy : the Journal of the American Society of Gene Therapy·Erkan Y OsmanChristian L Lorson
Nov 25, 2016·JCI Insight·Mahlet B AberaBarrington G Burnett
Apr 8, 2017·Science·Pengpeng BiEric N Olson
Jun 2, 2017·Nature Communications·Qiao ZhangSrihari C Sampath
Jun 2, 2017·Nature Communications·Malgorzata E QuinnDouglas P Millay
Jun 24, 2017·Biomedical Research·Daisuke TakeiHiroshi Takeshima
Aug 5, 2017·Disease Models & Mechanisms·Melissa BowermanUNKNOWN UK SMA Research Consortium
Aug 26, 2017·Scientific Reports·Kasey E MoritzBarrington G Burnett
Nov 2, 2017·The New England Journal of Medicine·Jerry R MendellBrian K Kaspar
Nov 2, 2017·The New England Journal of Medicine·Richard S FinkelUNKNOWN ENDEAR Study Group
Feb 2, 2018·Skeletal Muscle·Srihari C SampathDouglas P Millay
Feb 15, 2018·The New England Journal of Medicine·Eugenio MercuriUNKNOWN CHERISH Study Group

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antisense Oligonucleotides: ND

This feed focuses on antisense oligonucleotide therapies such as Inotersen, Nusinursen, and Patisiran, in neurodegenerative diseases including amyotrophic lateral sclerosis.

Cajal Bodies & Gems

Cajal bodies or coiled bodies are dense foci of coilin protein. Gemini of Cajal bodies, or gems, are microscopically similar to Cajal bodies. It is believed that Cajal bodies play important roles in RNA processing while gems assist the Cajal bodies. Find the latest research on Cajal bodies and gems here.

Antisense Oligonucleotide Therapies: ND

Antisense oligonucleotides are synthetic DNA oligomers that hybridize to a target RNA. This feed focuses on antisense oligonucleotide therapies such as Inotersen, Nusinursen, and Patisiran, in neurodegenerative diseases.