The Microtubule Network in Cardiac Mechanics and Local Translation

A primary focus of the Prosser Lab is on the microtubule cytoskeleton and its contribution to cardiac mechanics and mechanobiology.  The lab has combined super-resolution imaging with biophysical approaches to visualize the inner workings of the microtubule cytoskeleton in beating heart cells.  This exploration defined a previously unappreciated role for microtubules – and for post-translational modifications of tubulin - in regulating the mechanical and contractile properties of heart muscle cells (Robison Science 2016). The lab further found that suppressing post-translational detyrosination of microtubules can lower myocardial stiffness and robustly improve contractile function in cardiomyocytes from patients with heart failure (Chen et al., Nature Medicine 2018).  A subsequent series of publications and ongoing work is focused on the therapeutic potential of targeting these modified microtubules in diverse forms of heart failure.

More recently the lab has focused on fundamental mechanisms of cytoskeletal transport and their essential roles in cardiomyocyte homeostasis and growth.  The lab found that active transport of RNA and ribosomes among microtubule tracks is essential for the proper sub-cellular distribution the translational machinery, and that this governs highly localized translation in the heart muscle cell (Scarborough and Uchida Nature Communications 2021). These findings have broad implications for the local control of translation, for how sarcomeres are maintained and added, and how muscle cells remodel in hypertrophy and disease, an area of active investigation in the lab.

Ben Prosser est invité par Marie-Jo Moutin.