Microtubules’ role in heart cell contraction revealed

NIH | MAY 6, 2016

Researchers determined that microtubules, a type of molecular “strut,” play a key role in regulating contractile function in mouse and rat heart cells.

Microtubules in a heart cell at rest (top) and compressed during contraction (bottom). Dr. Ben Prosser, University of Pennsylvania

The heart is an organ made of muscle cells. Each individual heart cell, known as a cardiomyocyte, contains contractile units called sarcomeres that power its beating.

An organized network called the cytoskeleton helps cells maintain their shape and organization. Microtubules (MTs) are a major component of this cellular support structure. MTs can transmit mechanical signals and, like rods or struts, resist compression in contracting heart cells. How they perform these roles has been unclear.

A team led by Dr. Benjamin Prosser at the University of Pennsylvania set out to determine the role that MTs play in heart function.

The group used an advanced imaging approach to observe fluorescently tagged MTs inside beating mouse and rat heart cells in real time. They noted that as the cells contracted, the MTs “buckled” under the force in a pattern that coincided with contraction of the sarcomeres. Like a spring, the MTs returned to their normal shape between beats.

The scientists found that MTs are linked to sarcomeres through a lattice-like structure. This connection could be altered by removing the amino acid tyrosine from MTs. With more tyrosine attached, the MTs appeared to slide rather than buckle. This allowed the force-generating machinery inside the cells to shorten further and faster. When tyrosine was removed from MTs by a natural process called detyrosination, the MTs formed tighter, stiffer connections with the sarcomeres and restricted contraction.

To determine if this change might be associated with impaired heart function in humans, the team analyzed tissue from healthy donors and patients with heart disease. They found a correlation between lower MT tyrosine levels and decreased heart function.

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