In research published in the Journal of Cell Biology, scientists from the RIKEN Brain Science Institute in Japan have made important steps toward understanding how dynein--a "molecular motor"--walks along tube-like structures in the cell to move cellular cargo from the outer structures toward the cell body of neurons. The action of this molecule is important for a number of cell functions including axonal transport and chromosome segregation, and its dysfunction is known to lead to a congenital developmental brain disorder known as lissencephaly.
Though cells may look like shapeless blobs of liquid encased in a membrane, in fact they have a complex skeleton-like structure, known as the cytoskeleton, made up of filaments called microtubules. Motor proteins, which include dynein and kinesin, can move along these tubules to transport cargo into and out of the center of the cell.
The motor proteins use an energy-currency molecule, ATP, to power their movements along the microtubules. The motor proteins hydrolyze ATP to ADP, and convert the released chemical energy to mechanical energy which is used for movement. The mechanism is quite well understood for kinesin, but in the case of dynein, it has been difficult to explain how communication takes place between the site of microtubule binding and the site of ATP hydrolysis, which are relatively far from each other, separated by a stalk.
In the new research, performed in collaboration with several other institutes including the University of Osaka, Waseda, and Hosei University, the RIKEN scientists used cryo electron microscopy--where molecules are cooled to very low temperatures in the microscope--and examined the structure of dynein on the microtubule.
They showed that two specific amino acid residues on the microtubule structure, R403 and E416, are key to turning on the switch that is critical for the activation of the dynein motor--demonstrating that when mutations in these sequences are present, the dynein fails to achieve directional movement on the microtubule, ending up simply moving back and forth in a random fashion.
This lends weight to the idea, that has been generally accepted, that the motion of molecular motors is basically driven by random, Brownian motion, and that motors are able to move in one direction thanks to subtle changes in the strength of bonds at the motor-microtubule interface.
Additionally, the group discovered that turning on the mechanical switch at the motor-microtubule interface leads to ATP hydrolysis. Their results altogether indicate that the subtle structural changes in the bonds at the interface are transmitted through a small change in the structure of the stalk--there are two coils that link the two binding regions, and a small shift in the configuration of the coils gives the cue for ATP hydrolysis at the ATP binding site.
Seiichi Uchimura, the first author of the paper, said, "We were able to clearly demonstrate that the dynein molecular motor is activated by a 'switch' that controls mutual interactions between dynein and the microtubule. This is important, as a mutation in the structure of the switch has been demonstrated to cause lissencephaly, a congenital disorder."
According to Etsuko Muto, who led the research team, "In the future, we hope that further understanding the interplay between dynein and microtubule, as this could pave the way for therapies for these conditions."
Jens Wilkinson | EurekAlert!
Multi-institutional collaboration uncovers how molecular machines assemble
02.12.2016 | Salk Institute
Fertilized egg cells trigger and monitor loss of sperm’s epigenetic memory
02.12.2016 | IMBA - Institut für Molekulare Biotechnologie der Österreichischen Akademie der Wissenschaften GmbH
A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.
Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...
In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.
“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...
The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.
The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...
Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water
In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...
The efficiency of power electronic systems is not solely dependent on electrical efficiency but also on weight, for example, in mobile systems. When the weight of relevant components and devices in airplanes, for instance, is reduced, fuel savings can be achieved and correspondingly greenhouse gas emissions decreased. New materials and components based on gallium nitride (GaN) can help to reduce weight and increase the efficiency. With these new materials, power electronic switches can be operated at higher switching frequency, resulting in higher power density and lower material costs.
Researchers at the Fraunhofer Institute for Solar Energy Systems ISE together with partners have investigated how these materials can be used to make power...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
02.12.2016 | Medical Engineering
02.12.2016 | Agricultural and Forestry Science
02.12.2016 | Physics and Astronomy