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Location, location, location

Basic Science - Cardiac Diseases - Cardiac Hypertrophy


Location, location, location. You may have heard this mantra when talking to an agent about the home values. In a nutshell, it means homes can vary widely in value due to their location. Similar to homebuyers, cardiomyocytes do care about the location of protein translation. This new study provides a shift in thinking, as it indicates that the proper localization of translation – and not simply increased protein translation per se – is a critical determinant of cardiac hypertrophy. In the absence of microtubules, cardiomyocytes have no problem increasing hypertrophic gene expression or translation rate in response to a growth stimulus, but they cannot increase in size. The data presented in this study suggest that by orchestrating properly localized translation, microtubules serve as a necessary bridge to couple a hypertrophic stimulus and increased translation to productive cardiac growth.

While recent evidence has revealed the presence of both mRNAs and ribosomes to the sarcomere, supporting a model of local sarcomere synthesis and assembly 1, 2, the mechanism that moves the translational machinery and its potential contribution to hypertrophy, were largely unknown.

This story adds a relevant piece of information, showing a surprising and essential role of cardiomyocyte microtubules for controlling the key components of translation - mRNA and ribosomes - in space and time. Microtubules appear indispensable for the homeostatic distribution of the translational machinery, which has broad implications for protein quality control, sarcomere maintenance and remodeling. Sarcomeres are replaced weekly while cardiomyocytes have a lifespan of years 3, underscoring the need for such mechanisms. How microtubule-dependent trafficking is fine tuned to to match changing cardiac demand, and to what extent it contributes to the progression from hypertrophy to heart failure remains to be determined.

References


  1. Boateng, S. Y. & Goldspink, P. H. Assembly and maintenance of the sarcomere night and day. Cardiovasc. Res. 77, 667–675 (2008).
  2. Lewis, Y. E. et al. Localization of transcripts, translation, and degradation for spatiotemporal sarcomere maintenance. J. Mol. Cell Cardiol. 116, 16–28 (2018).
  3. Rudolph, F. et al. Resolving titin’s lifecycle and the spatial organization of protein turnover in mouse cardiomyocytes. Proc. Natl Acad. Sci. USA 116, 25126–25136 (2019).
The content of this article reflects the personal opinion of the author/s and is not necessarily the official position of the European Society of Cardiology.

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