Cofilin Loss in Drosophila Muscles Contributes to Muscle Weakness through Defective Sarcomerogenesis during Muscle Growth.

Cell Reports
Mridula BalakrishnanMary K Baylies

Abstract

Sarcomeres, the fundamental contractile units of muscles, are conserved structures composed of actin thin filaments and myosin thick filaments. How sarcomeres are formed and maintained is not well understood. Here, we show that knockdown of Drosophila cofilin (DmCFL), an actin depolymerizing factor, disrupts both sarcomere structure and muscle function. The loss of DmCFL also results in the formation of sarcomeric protein aggregates and impairs sarcomere addition during growth. The activation of the proteasome delays muscle deterioration in our model. Furthermore, we investigate how a point mutation in CFL2 that causes nemaline myopathy (NM) in humans affects CFL function and leads to the muscle phenotypes observed in vivo. Our data provide significant insights to the role of CFLs during sarcomere formation, as well as mechanistic implications for disease progression in NM patients.

References

Jan 1, 1990·Critical Reviews in Food Science and Nutrition·A M Pearson
Dec 1, 1987·The Journal of Cell Biology·J R Bamburg, D Bray
Dec 1, 1986·Journal of Muscle Research and Cell Motility·P BennettG Offer
Nov 1, 1967·Journal of Biochemistry·T MasakiS Ebashi
Oct 1, 1982·Journal of the Neurological Sciences·M YamaguchiT Oda
Jun 1, 1980·Experimental Cell Research·B M JockuschF G Jennekens
Jun 1, 1995·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·C S Farah, F C Reinach
Apr 28, 1995·Journal of Molecular Biology·S Labeit, B Kolmerer
May 10, 1994·Proceedings of the National Academy of Sciences of the United States of America·K A EdwardsD P Kiehart
Feb 1, 1996·Current Opinion in Cell Biology·V M Fowler
Jan 1, 1996·Annual Review of Cell and Developmental Biology·K M Ruppel, J A Spudich
Jan 5, 2000·Neuromuscular Disorders : NMD·C Wallgren-PetterssonA de la Chapelle
Mar 21, 2000·Biochimica Et Biophysica Acta·J R Sellers
May 3, 2001·American Journal of Human Genetics·B IlkovskiK N North
Jun 26, 2001·European Journal of Biochemistry·C ThirionH Lochmüller
Apr 30, 2002·Human Molecular Genetics·Brinda RavikumarDavid C Rubinsztein
Sep 27, 2002·Genesis : the Journal of Genetics and Development·John M Belote, Eric Fortier
Jul 6, 2004·Annals of Neurology·Pankaj B AgrawalAlan H Beggs
Sep 1, 2004·Neuromuscular Disorders : NMD·Carina Wallgren-PetterssonUNKNOWN ENMC International Consortium On Nemaline Myopathy
Dec 24, 2005·Human Molecular Genetics·Zdenek BergerDavid C Rubinsztein
Oct 5, 2006·Molecular Cell·Ernesto Andrianantoandro, Thomas D Pollard
May 12, 2007·Current Biology : CB·Alphée MichelotLaurent Blanchoin
Nov 3, 2007·Journal of Molecular Biology·Tesheka O StevensonGuy M Benian
Aug 14, 2008·Science Signaling·Jean M Sanger, Joseph W Sanger
Sep 17, 2008·Seminars in Cell & Developmental Biology·Ryan S Littlefield, Velia M Fowler
Feb 3, 2009·Advances in Experimental Medicine and Biology·Elisabeth Ehler, Mathias Gautel

❮ Previous
Next ❯

Methods Mentioned

BETA
nucleotide exchange
transmission electron microscopy
ubiquitination

Software Mentioned

Graph Pad Prism
Adobe Photoshop
Digital Micrograph
GraphPad Prism
Fiji
Leica Application Suite X
MacVector
Excel

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.