Detyrosinated microtubules buckle and bear load in contracting cardiomyocytes

Science. 2016 Apr 22;352(6284):aaf0659. doi: 10.1126/science.aaf0659.


The microtubule (MT) cytoskeleton can transmit mechanical signals and resist compression in contracting cardiomyocytes. How MTs perform these roles remains unclear because of difficulties in observing MTs during the rapid contractile cycle. Here, we used high spatial and temporal resolution imaging to characterize MT behavior in beating mouse myocytes. MTs deformed under contractile load into sinusoidal buckles, a behavior dependent on posttranslational "detyrosination" of α-tubulin. Detyrosinated MTs associated with desmin at force-generating sarcomeres. When detyrosination was reduced, MTs uncoupled from sarcomeres and buckled less during contraction, which allowed sarcomeres to shorten and stretch with less resistance. Conversely, increased detyrosination promoted MT buckling, stiffened the myocyte, and correlated with impaired function in cardiomyopathy. Thus, detyrosinated MTs represent tunable, compression-resistant elements that may impair cardiac function in disease.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Desmin / metabolism
  • Elasticity
  • Heart Failure / metabolism
  • Heart Failure / physiopathology
  • Humans
  • Male
  • Mice
  • Microtubules / metabolism*
  • Models, Biological
  • Myocardial Contraction*
  • Myocytes, Cardiac / metabolism
  • Myocytes, Cardiac / physiology*
  • Peptide Synthases / genetics
  • Peptide Synthases / metabolism
  • Protein Processing, Post-Translational*
  • RNA, Small Interfering / genetics
  • Rats
  • Rats, Sprague-Dawley
  • Sarcomeres / metabolism
  • Tubulin / metabolism*
  • Tyrosine / metabolism*


  • Desmin
  • RNA, Small Interfering
  • Tubulin
  • tyrosine-tubulin
  • Tyrosine
  • Peptide Synthases
  • tyrosyltubulin ligase