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

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


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.


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


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

light microscopy
confocal microscopy

Related Concepts

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

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