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).
Possible models for the bi-directional movement observed in the dynein-dynactin molecular motor along microtubules. A) Random, diffusive motions; B) Flexible rotation of the dynein ring; and C) Steps dictated by the microtubule lattice. Credit: Jennifer L. Ross, PhD, University of Pennsylvania School of Medicine; Nature Cell Biology
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.'" Goldman and Holzbaur suggest that the ability of the dynein-dynactin motor to move in both directions along the microtubule may provide the necessary maneuvering ability to allow for effective long distance transport.
Earlier this year, as reported in The Journal of Cell Biology, researchers in Holzbaur's lab found that a mutation in dynactin leads to degeneration of motor neurons, the hallmark of motor neuron disease. This mutation decreases the efficiency of the dynein-dynactin motor in "taking out the trash" of the cell, and thus leads to the accumulation of misfolded proteins in the cell, which may in turn lead to the degeneration of the neuron.
Scientists are now finding that many other molecular motors are remarkably flexible in their behavior. In several further papers published in the Proceedings of the National Academy of Sciences and The EMBO Journal, Goldman and colleagues at the University of Illinois found that a "local delivery" motor, termed myosin V, moves cargo with a variable path short distances along another type of cellular track called actin. This flexibility could help myosin V navigate crowded regions of the cell where the actin filaments criss-cross and where other cellular components would otherwise pose an impediment to motion. Defects in myosin V function also result in neurological defects.
Most of these molecular motors are associated with specific diseases or developmental defects, so understanding the puzzling aspects of their behavior in detail is necessary for building nanotechnological machines that, for example, could replace defective motors. "The ultimate goal is to find ways to treat motor neuron disease as well as other diseases that involve cellular motors and also construct nano-scale machines based on these biological motors," says Goldman.
Karen Kreeger | EurekAlert!
Nesting aids make agricultural fields attractive for bees
20.07.2017 | Julius-Maximilians-Universität Würzburg
The Kitchen Sponge – Breeding Ground for Germs
20.07.2017 | Hochschule Furtwangen
Physicists have developed a new technique that uses electrical voltages to control the electron spin on a chip. The newly-developed method provides protection from spin decay, meaning that the contained information can be maintained and transmitted over comparatively large distances, as has been demonstrated by a team from the University of Basel’s Department of Physics and the Swiss Nanoscience Institute. The results have been published in Physical Review X.
For several years, researchers have been trying to use the spin of an electron to store and transmit information. The spin of each electron is always coupled...
What is the mass of a proton? Scientists from Germany and Japan successfully did an important step towards the most exact knowledge of this fundamental constant. By means of precision measurements on a single proton, they could improve the precision by a factor of three and also correct the existing value.
To determine the mass of a single proton still more accurate – a group of physicists led by Klaus Blaum and Sven Sturm of the Max Planck Institute for Nuclear...
The research team of Prof. Dr. Oliver Einsle at the University of Freiburg's Institute of Biochemistry has long been exploring the functioning of nitrogenase....
A one trillion tonne iceberg - one of the biggest ever recorded -- has calved away from the Larsen C Ice Shelf in Antarctica, after a rift in the ice,...
Physics supports biology: Researchers from PTB have developed a model system to investigate friction phenomena with atomic precision
Friction: what you want from car brakes, otherwise rather a nuisance. In any case, it is useful to know as precisely as possible how friction phenomena arise –...
19.07.2017 | Event News
12.07.2017 | Event News
12.07.2017 | Event News
20.07.2017 | Information Technology
20.07.2017 | Materials Sciences
20.07.2017 | Physics and Astronomy