Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Discovery of agile molecular motors could aid in treating motor neuron diseases

19.07.2006
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).


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!
Further information:
http://www.uphs.upenn.edu/

More articles from Life Sciences:

nachricht Meadows beat out shrubs when it comes to storing carbon
23.11.2017 | Norwegian University of Science and Technology

nachricht Migrating Cells: Folds in the cell membrane supply material for necessary blebs
23.11.2017 | Westfälische Wilhelms-Universität Münster

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Frictional Heat Powers Hydrothermal Activity on Enceladus

Computer simulation shows how the icy moon heats water in a porous rock core

Heat from the friction of rocks caused by tidal forces could be the “engine” for the hydrothermal activity on Saturn's moon Enceladus. This presupposes that...

Im Focus: Nanoparticles help with malaria diagnosis – new rapid test in development

The WHO reports an estimated 429,000 malaria deaths each year. The disease mostly affects tropical and subtropical regions and in particular the African continent. The Fraunhofer Institute for Silicate Research ISC teamed up with the Fraunhofer Institute for Molecular Biology and Applied Ecology IME and the Institute of Tropical Medicine at the University of Tübingen for a new test method to detect malaria parasites in blood. The idea of the research project “NanoFRET” is to develop a highly sensitive and reliable rapid diagnostic test so that patient treatment can begin as early as possible.

Malaria is caused by parasites transmitted by mosquito bite. The most dangerous form of malaria is malaria tropica. Left untreated, it is fatal in most cases....

Im Focus: A “cosmic snake” reveals the structure of remote galaxies

The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.

Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...

Im Focus: Visual intelligence is not the same as IQ

Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.

That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...

Im Focus: Novel Nano-CT device creates high-resolution 3D-X-rays of tiny velvet worm legs

Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.

During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Ecology Across Borders: International conference brings together 1,500 ecologists

15.11.2017 | Event News

Road into laboratory: Users discuss biaxial fatigue-testing for car and truck wheel

15.11.2017 | Event News

#Berlin5GWeek: The right network for Industry 4.0

30.10.2017 | Event News

 
Latest News

Underwater acoustic localization of marine mammals and vehicles

23.11.2017 | Information Technology

Enhancing the quantum sensing capabilities of diamond

23.11.2017 | Physics and Astronomy

Meadows beat out shrubs when it comes to storing carbon

23.11.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>