Characterization of a hypercontraction-induced myopathy in Drosophila caused by mutations in Mhc

The Journal of Cell Biology
Enrico S Montana, J Troy Littleton

Abstract

The Myosin heavy chain (Mhc) locus encodes the muscle-specific motor mediating contraction in Drosophila. In a screen for temperature-sensitive behavioral mutants, we have identified two dominant Mhc alleles that lead to a hypercontraction-induced myopathy. These mutants are caused by single point mutations in the ATP binding/hydrolysis domain of Mhc and lead to degeneration of the flight muscles. Electrophysiological analysis in the adult giant fiber flight circuit demonstrates temperature-dependent seizure activity that requires neuronal input, as genetic blockage of neuronal activity suppresses the electrophysiological seizure defects. Intracellular recordings at the third instar neuromuscular junction show spontaneous muscle movements in the absence of neuronal stimulation and extracellular Ca2+, suggesting a dysregulation of intracellular calcium homeostasis within the muscle or an alteration of the Ca2+ dependence of contraction. Characterization of these new Mhc alleles suggests that hypercontraction occurs via a mechanism, which is molecularly distinct from mutants identified previously in troponin I and troponin T.

References

May 1, 1971·Proceedings of the National Academy of Sciences of the United States of America·D T SuzukiR Williamson
Jan 1, 1994·Methods in Cell Biology·E A FyrbergK VijayRaghavan
Apr 25, 1995·Proceedings of the National Academy of Sciences of the United States of America·I RaymentN D Epstein
May 26, 1995·Journal of Molecular Biology·William A KronertSanford I Bernstein
Aug 1, 1994·Journal of Comparative Physiology. A, Sensory, Neural, and Behavioral Physiology·B A StewartC F Wu
May 22, 1998·Journal of Molecular Biology·S S Lehrer, Michael A Geeves
Mar 23, 1999·The Journal of Cell Biology·William A KronertSanford I Bernstein
Apr 28, 1999·International Review of Neurobiology·L S Gramates, V Budnik
Apr 1, 2000·Clinical and Experimental Pharmacology & Physiology·G D Lamb
Jul 19, 2000·Journal of Biomechanics·A F Huxley
Dec 16, 2000·Trends in Biochemical Sciences·T D Pollard
May 10, 2001·Trends in Cardiovascular Medicine·A FerrusA Hernández-Hernández
May 22, 2001·Molecular Biology of the Cell·B NaimiJohn C Sparrow
Dec 18, 2001·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·J O Vigoreaux
Jan 16, 2003·Physiology & Behavior·Robert E Poage, Stephen D Meriney
Nov 1, 2003·Annals of the New York Academy of Sciences·Robert L Ruff
Dec 23, 2003·The Journal of Comparative Neurology·Patricia K RivlinDavid L Deitcher

Citations

Aug 14, 2012·Nature Cell Biology·Mary PinesGuy Tanentzapf
Oct 9, 2015·Molecular Biology of the Cell·Guðlaug Katrín HákonardóttirGuy Tanentzapf
Jan 10, 2012·Journal of Molecular Biology·William A KronertSanford I Bernstein
Mar 15, 2016·Cell Reports·Katerina M VakaloglouChristos G Zervas
Feb 23, 2012·Scientific Reports·April K MarroneHalyna R Shcherbata
Nov 28, 2018·Journal of Cell Science·Nicole GreenErika R Geisbrecht
Jul 1, 2005·Physiological Reviews·Scott L Hooper, Jeffrey B Thuma

Methods Mentioned

BETA
light microscopy
PCR
confocal microscopy

Related Concepts

Adenosine Triphosphate, Chromium Ammonium Salt
Calcium
Drosophila
Flight, Animal
Inotropism
Point Mutation
Soleus Muscle Structure
Myosin Heavy Chains
Drosophila melanogaster Proteins

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.

Alzheimer's Disease: MS4A

Variants within the membrane-spanning 4-domains subfamily A (MS4A) gene cluster have recently been implicated in Alzheimer's disease in genome-wide association studies. Here is the latest research on Alzheimer's disease and MS4A.

Pediculosis pubis

Pediculosis pubis is a disease caused by a parasitic insect known as Pthirus pubis, which infests human pubic hair, as well as other areas with hair including eye lashes. Here is the latest research.

Rh Isoimmunization

Rh isoimmunization is a potentially preventable condition that occasionally is associated with significant perinatal morbidity or mortality. Discover the latest research on Rh Isoimmunization here.

Genetic Screens in iPSC-derived Brain Cells

Genetic screening is a critical tool that can be employed to define and understand gene function and interaction. This feed focuses on genetic screens conducted using induced pluripotent stem cell (iPSC)-derived brain cells. It also follows CRISPR-Cas9 approaches to generating genetic mutants as a means of understanding the effect of genetics on phenotype.

Enzyme Evolution

This feed focuses on molecular models of enzyme evolution and new approaches (such as adaptive laboratory evolution) to metabolic engineering of microorganisms. Here is the latest research.

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.

Pharmacology of Proteinopathies

This feed focuses on the pharmacology of proteinopathies - diseases in which proteins abnormally aggregate (i.e. Alzheimer’s, Parkinson’s, etc.). Discover the latest research in this field with this feed.

Alignment-free Sequence Analysis Tools

Alignment-free sequence analyses have been applied to problems ranging from whole-genome phylogeny to the classification of protein families, identification of horizontally transferred genes, and detection of recombined sequences. Here is the latest research.