Davis J, Davis LC, Correll RN, Makarewich CA, Schwanekamp JA, Moussavi-Harami F, Wang D, York AJ, Wu H, Houser SR, Seidman CE, Seidman JG, Regnier M, Metzger JM, Wu JC, Molkentin JD. A Tension-Based Model Distinguishes Hypertrophic versus Dilated Cardiomyopathy. Cell. 2016 May 19;165(5):1147-59.
During cardiac disease the heart changes form, growing larger and more muscular or dilating with the walls becoming stretched and thin. The processes responsible for these different pathogenic pathways remain obscure. This manuscript defines one of the underlying mechanisms which dictates the pathway taken. By using genetically engineered mouse hearts, the paper shows that muscle tension can be the major force in dictating the choice and predicts whether a dilated or hypertrophy heart will result from how a particular gene mutation changes how the muscle develops internal tension during contraction.
Gupta MK, McLendon PM, Gulick J, James J, Khalili K, Robbins J. UBC9-Mediated Sumoylation Favorably Impacts Cardiac Function in Compromised Hearts. Circ Res. 2016 Jun 10;118(12):1894-905.
The process of cellular self-digestion, called autophagy, is critical for normal cell function and is often altered in cardiovascular disease. We have found the modification of cardiac proteins during development of disease can have significant functional consequences. One of these processes adds small peptide groups to the existing protein, modifying it and changing its activity. This process, called SUMOylation, can in cardiac disease result in a heart that is more resistant to the pathogenic stimuli. Modulating this pathway’s activity may represent a novel strategy for increasing autophagic flux and ameliorating morbidity in proteotoxic cardiac disease.
Millay DP, Gamage DG, Quinn ME, Min YL, Mitani Y, Bassel-Duby R, Olson EN. Structure-function analysis of myomaker domains required for myoblast fusion. Proc Natl Acad Sci U S A. 2016 Feb 23;113(8):2116-21.
Skeletal muscle forms from the fusion of stem cells during development and regeneration. Manipulation of stem cell fusion could offer strategies to treat muscle diseases such as muscular dystrophy and age-related atrophy. Myomaker is a membrane protein that governs muscle cell fusion, however the details of how this protein functions remains unknown. In this manuscript we show that myomaker contains seven membrane-spanning regions with an intracellular C-terminal tail that is necessary for fusion. These results are an important first step to understand fusion and how it might be therapeutically controlled to mitigate muscle diseases.