Detyrosinated microtubules buckle and bear load in contracting cardiomyocytes.
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.
Department of Physiology, Pennsylvania Muscle Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Patrick
P
Robison
Department of Materials Science and Engineering, University of Pennsylvania School of Engineering and Applied Science, Philadelphia, PA 19104, USA.
Matthew A
MA
Caporizzo
Department of Materials Science and Engineering, University of Pennsylvania School of Engineering and Applied Science, Philadelphia, PA 19104, USA.
Hossein
H
Ahmadzadeh
Department of Physiology, Pennsylvania Muscle Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Alexey I
AI
Bogush
Department of Physiology, Pennsylvania Muscle Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Christina Yingxian
CY
Chen
Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
Kenneth B
KB
Margulies
Department of Materials Science and Engineering, University of Pennsylvania School of Engineering and Applied Science, Philadelphia, PA 19104, USA.
Vivek B
VB
Shenoy
Department of Physiology, Pennsylvania Muscle Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA. bpros@mail.med.upenn.edu.
Benjamin L
BL
Prosser
D000818:Animals; D003893:Desmin / Q000378:metabolism; D004548:Elasticity; D006333:Heart Failure / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D008297:Male; D051379:Mice; D008870:Microtubules / Q000378:metabolism*; D008954:Models, Biological; D009200:Myocardial Contraction; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000502:physiology*; D010453:Peptide Synthases / Q000235:genetics / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012518:Sarcomeres / Q000378:metabolism; D014404:Tubulin / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism*
D003893:Desmin; D034741:RNA, Small Interfering; D014404:Tubulin; C039520:tyrosine-tubulin; D014443:Tyrosine; D010453:Peptide Synthases; C023213:tyrosyltubulin ligase