Altered expression of tropomodulin in cardiomyocytes disrupts the sarcomeric structure of myofibrils

Circulation Research
M SussmanLarry Kedes

Abstract

Tropomodulin is a tropomyosin-binding protein that terminates "pointed-end" actin filament polymerization. To test the hypothesis that regulation of tropomodulin:actin filament stoichiometry is critical for maintenance of actin filament length, tropomodulin levels were altered in cells by infection with recombinant adenoviral expression vectors, which produce either sense or antisense tropomodulin mRNA. Neonatal rat cardiomyocytes were infected, and sarcomeric actin filament organization was examined. Confocal microscopy indicated that overexpression of tropomodulin protein shortened actin filaments and caused myofibril degeneration. In contrast, decreased tropomodulin content resulted in the formation of abnormally long actin filament bundles. Despite changes in myofibril structure caused by altered tropomodulin expression, total protein turnover of the cardiomyocytes was unaffected. Biochemical analyses of infected cardiomyocytes indicated that changes in actin distribution, rather than altered actin content, accounted for myofibril reorganization. Ultrastructural analysis showed thin-filament disarray and revealed the presence of leptomeres after tropomodulin overexpression. Tropomodulin-mediated effects constitute a novel m...Continue Reading

References

Sep 1, 1979·Proceedings of the National Academy of Sciences of the United States of America·H TowbinJ Gordon
Aug 1, 1978·Okajimas Folia Anatomica Japonica·T OnoK Yasuda
May 5, 1977·Nature·T F Robinson, S Winegrad
Jan 1, 1990·Journal of Molecular Neuroscience : MN·M A SussmanV M Fowler
Oct 1, 1987·The Journal of Clinical Investigation·N H BishopricC P Ordahl
Jan 1, 1973·Tissue & Cell·A F Miranda, G C Godman
Jan 1, 1983·Methods in Enzymology·J S Morrow, W B Haigh
Dec 1, 1994·The Journal of Cell Biology·A WeberV M Fowler
Jan 1, 1995·The Journal of Cell Biology·D A SchaferJ A Cooper
Jul 15, 1994·Brain Research. Developmental Brain Research·M A SussmanS S Schreiber
Apr 1, 1996·The American Journal of Physiology·D G SimpsonA M Samarel
Feb 14, 1998·The Journal of Clinical Investigation·M A SussmanT R Kimball
Jan 1, 1991·Methods in Molecular Biology·F L Graham, L Prevec

❮ Previous
Next ❯

Citations

Oct 24, 2003·Trends in Cell Biology·Robert S Fischer, Velia M Fowler
Jun 15, 2005·Trends in Cell Biology·Peter W GunningEdna C Hardeman
Jun 12, 2003·Molecular and Cellular Neurosciences·Patrick R CoxHuda Y Zoghbi
Jan 10, 2013·Nature Reviews. Molecular Cell Biology·David S Gokhin, Velia M Fowler
Feb 17, 2009·Biochemistry. Biokhimii︠a︡·A S Kostyukova
Jan 19, 1999·Annual Review of Cell and Developmental Biology·R Littlefield, V M Fowler
Jul 27, 2002·Annual Review of Cell and Developmental Biology·Kathleen A ClarkCarol C Gregorio
Feb 3, 2000·Proceedings of the National Academy of Sciences of the United States of America·T TaigenJ D Molkentin
Sep 4, 2007·American Journal of Physiology. Heart and Circulatory Physiology·Elisabeth A Gustafson-WagnerJim J-C Lin
Aug 12, 2008·Human Molecular Genetics·Michael P WalkerA Gregory Matera
Oct 21, 2011·Journal of Biomedicine & Biotechnology·David S Gokhin, Velia M Fowler
May 31, 2012·Cellular and Molecular Life Sciences : CMLS·Mirco MüllerHans Georg Mannherz
May 16, 2001·The Journal of Cell Biology·E EhlerJ C Perriard
Dec 6, 2003·The Journal of Cell Biology·Kimberly L Fritz-SixVelia M Fowler
Sep 15, 2005·The Journal of Cell Biology·Abigail S McElhinnyCarol C Gregorio
Apr 7, 2010·The Journal of Cell Biology·David S GokhinVelia M Fowler
Sep 17, 2003·The Journal of Cell Biology·Ryan E MudryCarol C Gregorio
May 26, 2010·The Journal of Cell Biology·Christopher T PappasCarol C Gregorio
Feb 14, 2016·Biochimica Et Biophysica Acta·Mert ColpanAlla S Kostyukova
Oct 22, 2015·Proceedings of the National Academy of Sciences of the United States of America·Christopher T PappasCarol C Gregorio
Oct 19, 2004·Seminars in Nephrology·Laurence KedesYasuo Hamamori
Nov 29, 2005·European Journal of Heart Failure·Michaela AdamcováVladimír Gersl
Oct 4, 2006·Micron : the International Research and Review Journal for Microscopy·Eduard I DedkovAndrei B Borisov
Feb 17, 2006·Trends in Cell Biology·Robert Horowits
Dec 11, 1999·Journal of Molecular and Cellular Cardiology·D J MilnerY Capetanaki
Jan 13, 2006·Current Biology : CB·Velia M FowlerRobert S Fischer
Apr 20, 2002·Biophysical Journal·Norma J Greenfield, Velia M Fowler
Oct 18, 2014·Frontiers in Physiology·David S GokhinVelia M Fowler
Mar 26, 2004·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Elisabeth EhlerJean-Claude Perriard
Jun 5, 2001·Nature Cell Biology·R LittlefieldV M Fowler

❮ Previous
Next ❯

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.