Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Biologists Capture Cell’s Elusive ‘Motor’ on Videotape

19.05.2011
In basic research with far-reaching impact, cell biologists Wei-Lih Lee and Steven Markus report in an article released today in Developmental Cell, with videos, that they have solved one of the fundamental questions in stem cell division: How dynein, the cell’s two-part, nano-scale “mitotic motor,” positions itself to direct the dividing process.

Their experiments can be likened to restoring never-before-seen footage to a classic film. What’s more, Lee says that footage is crucial to the plot and helps to explain the entire production.

Further, because the same polarization processes as those Lee and colleagues observed in budding yeast occur during asymmetric division of analogous human stem cells, the significance of this discovery is enormous. It should advance understanding of such serious neurological disorders as human lissencephaly, a rare brain formation disorder resulting in a “smooth” brain without folds and grooves, he adds.

In neurons, dynein’s major role is to carry waste products from the nerve terminal to the cell body. If this transport goes awry, neurons degenerate, leading to such diseases as Alzheimer’s and ALS. “Our discovery solves a huge mystery about how dynein works during asymmetric cell divisions, such as those in stem cells, and confirms to us that the regulation we see for yeast dynein is common to mammalian dynein,” Lee says.

In non-neurons, such as dividing stem cells, dynein performs dozens of division-related processes, so many in fact that it’s said to “promiscuously” associate with many different cellular cargoes, Lee adds. He and Markus, with undergraduate Jesse Punch, are known for their previous discoveries of how dynein controls the early steps. They belong to the Morrill Motor & Mitosis group in the UMass Amherst biology department.

As they explain, asymmetric division in stem cells is specialized for generating different cell types that will develop into specific tissues such as skin, heart and kidney. Non-stem cell division is simpler and usually symmetrical.

Dynein, the transport-directing two-part motor and cargo molecule, controls the first steps in asymmetric division, aligning and orienting the chromosome-separating spindle apparatus. When the cell is about to divide, dynein rides at the tips of track-like microtubules to a spot in the outer cell periphery, known as the cortex. Dynein’s tail end binds and offloads the motor to the cortex, anchoring the molecule to the membrane at a point opposite the spindle apparatus.

With this, dynein acts like a tent stake to hold and pull the spindle apparatus as it moves to a new location to form two unequal daughter cells. Lee and colleagues also knew from earlier work that dynein’s motor and tail parts inhibit or mask each other while moving along the microtubule, so no accidental interactions can take place. When the microtubule-guided dynein reaches the cortex and is ready to offload, it unmasks.

What have been completely hidden up to now are the events occurring between the microtubule ride and anchoring in the cell membrane. “This is a long-standing mystery,” Lee says. “We could see the masked dynein traveling at the tips of the microtubules, but no one had ever seen it delivered to the cortex.”

To trick dynein into revealing the steps in offloading, Lee and Markus engineered an 11-nanometer-long peptide spacer roughly equal to the motor section’s diameter. Like a bolster pillow slipped between two halves of a clam shell, it increases the space between the motor and the cargo-attaching tail but still allows the parts to stay physically connected. The researchers then used a conventional fluorescence microscope to observe each part’s separate activity with the spacer in place.

The setup worked better than they dared to hope. The mutants (those with an engineered peptide spacer) retained normal motor activity and allowed an enhanced view of offloading. Specifically, Lee says, “With that little forced physical distance between the motor and tail, we expected that both parts would react independently with respect to microtubule tips and the offloading sites, which is what we observed.”

“What we didn’t expect,” he continues, “is the ability to actually observe the delivery process. It was a complete surprise and a eureka moment for us to witness a hypothesis supported by direct evidence for the first time. Now we know how it occurs.”

The research team conducted further experiments to compare mutant with normal dynein under a Total Internal Reflection Fluorescence (TIRF) microscope, allowing them to visualize single dynein molecule behavior, Lee points out. These confirm that the elegantly designed peptide spacer disrupted just a single variable, its deployment in the cell, and did not globally disrupt the motor chemical activity.

Overall, results clearly show microtubule-mediated delivery is tightly controlled by a masking mechanism within the dynein molecule, Lee says, which now leads to a lot more questions. His team is already working on at least two: What molecule is doing the un-masking in the various microtubule-mediated polarization processes? And, once offloaded from the microtubule tip, how is the motor “turned on” at the cortex?

Link to journal article and video: http://www.cell.com/developmental-cell/abstract/S1534-5807%2811%2900162-6

Wei-Lih Lee
413-545-2944
wlee@bio.umass.edu

Wei-Lih Lee | Newswise Science News
Further information:
http://www.umass.edu

More articles from Life Sciences:

nachricht 'Y' a protein unicorn might matter in glaucoma
23.10.2017 | Georgia Institute of Technology

nachricht Microfluidics probe 'cholesterol' of the oil industry
23.10.2017 | Rice University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Salmonella as a tumour medication

HZI researchers developed a bacterial strain that can be used in cancer therapy

Salmonellae are dangerous pathogens that enter the body via contaminated food and can cause severe infections. But these bacteria are also known to target...

Im Focus: Neutron star merger directly observed for the first time

University of Maryland researchers contribute to historic detection of gravitational waves and light created by event

On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...

Im Focus: Breaking: the first light from two neutron stars merging

Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.

Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....

Im Focus: Smart sensors for efficient processes

Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).

When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...

Im Focus: Cold molecules on collision course

Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.

How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

3rd Symposium on Driving Simulation

23.10.2017 | Event News

ASEAN Member States discuss the future role of renewable energy

17.10.2017 | Event News

World Health Summit 2017: International experts set the course for the future of Global Health

10.10.2017 | Event News

 
Latest News

Microfluidics probe 'cholesterol' of the oil industry

23.10.2017 | Life Sciences

Gamma rays will reach beyond the limits of light

23.10.2017 | Physics and Astronomy

The end of pneumonia? New vaccine offers hope

23.10.2017 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>