Publication Date:
2016-04-23
Description:
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 alpha-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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Robison, Patrick -- Caporizzo, Matthew A -- Ahmadzadeh, Hossein -- Bogush, Alexey I -- Chen, Christina Yingxian -- Margulies, Kenneth B -- Shenoy, Vivek B -- Prosser, Benjamin L -- HL089847/HL/NHLBI NIH HHS/ -- HL105993/HL/NHLBI NIH HHS/ -- R00-HL114879/HL/NHLBI NIH HHS/ -- R01EB017753/EB/NIBIB NIH HHS/ -- T32AR053461-09/AR/NIAMS NIH HHS/ -- T32HL007954/HL/NHLBI NIH HHS/ -- New York, N.Y. -- Science. 2016 Apr 22;352(6284):aaf0659. doi: 10.1126/science.aaf0659.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Physiology, Pennsylvania Muscle Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA. ; Department of Materials Science and Engineering, University of Pennsylvania School of Engineering and Applied Science, Philadelphia, PA 19104, USA. ; Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA. ; Department of Physiology, Pennsylvania Muscle Institute, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA. bpros@mail.med.upenn.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/27102488" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Desmin/metabolism
;
Elasticity
;
Heart Failure/metabolism/physiopathology
;
Humans
;
Male
;
Mice
;
Microtubules/*metabolism
;
Models, Biological
;
*Myocardial Contraction
;
Myocytes, Cardiac/metabolism/*physiology
;
Peptide Synthases/genetics/metabolism
;
*Protein Processing, Post-Translational
;
RNA, Small Interfering/genetics
;
Rats
;
Rats, Sprague-Dawley
;
Sarcomeres/metabolism
;
Tubulin/*metabolism
;
Tyrosine/*metabolism
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
Permalink
