Microtubule dynamics control the direction of cardiomyocyte growth

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Abstract
The adult heart grows by the addition of sarcomeres along the length or width of individual cardiomyocytes, yet how directional growth is spatially coordinated remains unclear. We found that microtubule dynamics could act as a toggle to direct cardiomyocyte growth. Increasing microtubule stability drove cellular widening, concomitant with redirecting messenger RNA (mRNA) export and translation along the width of the cell and reinforcement of the intercalated disc. Conversely, decreasing microtubule stability promoted cellular lengthening, disrupting the intercalated disc and biasing translation and incorporation of new sarcomeric protein toward this structure. Notably, disrupting intercalated disc adhesion was sufficient for cardiomyocyte elongation yet dispensable for cardiomyocyte widening. Thus, the heart coordinates local translation and structural remodeling to orchestrate bidirectional growth.
Funding Information
  • National Institutes of Health (R01-HL133080)
  • National Institutes of Health (HL149891)
  • National Institutes of Health (F32 HL158027-01)
  • National Institutes of Health (T32 AR053461)
  • National Institutes of Health (T32 HL007843)
  • National Institutes of Health (HL149891)
  • National Institutes of Health (FHL182030A)
  • American Heart Association (24CDA1267507)
  • Fondation Leducq (20CVD01)
  • Fondation Leducq (20CVD01)
  • Center for Engineering MechanoBiology, National Science Foundation’s Science and Technology Center program (15-48571)
  • United States-Israel Binational Science Foundation (2019126)
  • Center for Engineering MechanoBiology, National Science Foundation’s Science and Technology Center program (15-48571)

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