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Discovery of Agile Molecular Motors Could Aid in Treating Motor Neuron Diseases

Over the last several months, the labs of Yale Goldman, MD, PhD, Director of the Pennsylvania Muscle Institute at the University of Pennsylvania School of Medicine,// and Erika Holzbaur, PhD, Professor of Physiology, have published a group of papers that, taken together, show proteins that function as molecular motors are surprisingly flexible and agile, able to navigate obstacles within the cell. These observations could lead to better ways to treat motor neuron diseases.

Motor neuron diseases are a group of progressive neurological disorders that destroy motor neurons, the cells that control voluntary muscles for such activities as speaking, walking, breathing, and swallowing. When these neurons die, the muscle itself atrophies. A well-known motor neuron disease is amyotrophic lateral sclerosis (ALS, commonly known as Lou Gehrig’s disease).

Using a specially-constructed microscope that allows researchers to observe the action of one macromolecule at a time, the team found that a protein motor is able to move back and forth along a microtubule – a molecular track – rather than in one direction, as previously thought. They report their findings in a recent issue of Nature Cell Biology. The proteins in this motor, dynein and dynactin, are the “long-distance truckers” of the cell: working together, they are responsible for transporting cellular cargo from the periphery of a cell toward its nucleus.

“My lab concentrates on the cellular and genetic aspects of the dynein-dynactin motor, while Yale’s group delves into the mechanics of the motor itself,” says Holzbaur. “We’re deconstructing the system to understand how it all works in a living cell. In the lab, we start with a clean microtubule with a motor walking across it, but in the cell it’s different: microtubules are packed together, with proteins studded along them, and cellular organelles and mitochondria are crammed in. The motor needs to maneuver around those ‘obstructions.’”
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