Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Multi-disciplinary Penn Research Identifies Protein Required for Cell Movement

13.08.2013
Both basic scientists and clinicians have an interest in how the cells of our body move.

Cells must be mobile in order for organisms to grow, to heal, to transmit information internally, to mount immune responses and to conduct a host of other activities necessary for survival. But if cell mobility is unregulated, tumors can grow and spread throughout the body.


An electron microscope (left) and mathematical simulations (right) show Exo70-induced membrane reshaping.

A new multi-disciplinary study by University of Pennsylvania researchers has now illuminated a crucial step in the process of cell movement. The protein they examined, Exo70, induces a reshaping of the cell’s plasma membrane, a necessary step in how a cell migrates from one location to another.

The findings deepen the understanding of how cells initiate movement, and they have implications for conditions dependent on cell migration, including cancer.

The research, published in the journal Developmental Cell, was co-led by graduate students Yuting Zhao and Jianglan Liu, both members of senior author Wei Guo’s lab in Penn’s School of Arts and Sciences’ Department of Biology. Liu is now a postdoctoral fellow at the Wistar Institute. The work involved a collaboration with researchers at Penn’s Perelman School of Medicine and School of Engineering and Applied Science.

Previous research on cell migration had focused on actin, a protein that forms filaments and branches and is known to play a role in a variety of activities, including those that involve remodeling a cell’s shape. But Guo and other scientists believed there had to be other factors aiding the reshaping of cellular membranes.

“The plasma membrane is not a rubber band,” Guo said. “It’s hard to imagine actin just pushing it to change its shape. There had to be a mechanism to accommodate the actin, otherwise the membrane would be ruptured.”

That’s when Guo’s team thought of Exo70. His lab is focused on exocytosis, or the organized process by which cells carry proteins to the membrane in vesicles and then release important molecules such as hormones and neurotransmitters to travel elsewhere in the body. A structure made up several proteins, called the exocyst, helps mediate this process. Previous work by Guo and colleagues found that the exocyst is also involved in cell migration. Last year his lab published a paper, also with Liu and Zhao as lead authors, showing that Exo70, a component of the exocyst, stimulates actin structural changes at the leading edge of migrating cells.

In the current study, Zhao, Liu, Guo and colleagues wanted to more deeply examine what Exo70 was doing in the cell and how it was doing it. Using electron microscopy, they first found that Exo70 “bends” the membranes to generate high-curvature tubules. In addition, the presence of Exo70 in cells led to the creation of protrusions on the membranes. They also found that Exo70 formed complexes of at least two copies of the protein, known as oliogmers.

Using mathematical models, the researchers teamed with Ravi Radhakrishnan’s group in Penn Engineering to study how the curvature of these protrusions formed. They confirmed that their simulations matched up with what they were observing Exo70 do under the microscope.

Then, using time-lapse microscopy, they found that Exo70 generated protrusions in the membrane that were later filled with actin.

“We call it the empty glove,” Guo said. “Exo70 is the glove, and actin acts like fingers that push in and fill the empty pockets.”

Exo70 proteins that were mutated so they couldn’t form oligomers were unable to effectively migrate, the researchers discovered, underscoring the importance of the molecule in helping cells make directed movements.

“This gives us a new understanding of the mechanism of cell migration,” Guo said. “Studies in the field have been very much focused on actin, but our findings emphasize the importance of the membrane component in cell motility.”

Guo and colleagues are pursuing further studies of Exo70 to consider a possible role for it in the uncontrolled growth and metastasis seen in many forms of cancer.

Three of Penn’s schools, including five different departments, collaborated on this publication.

Additional authors in the School of Arts and Sciences included Changson Yang and Tatyana Svitkina of the Department of Biology and Benjamin R. Capraro and Tobias Baumgart of the Department of Chemistry. The School of Engineering and Applied Science’s Ryan P. Bradley of the Department of Chemical and Biomolecular Engineering, N. Ramakrishnan of the Department of Bioengineering and Ravi Radhakrishnan, who has affiliations in both departments, contributed. And Xiaowei Xu from the Perelman School of Medicine’s Department of Pathology and Laboratory Medicine was also a coauthor.

The research was supported by the National Institutes of Health.

Katherine Unger Baillie | EurekAlert!
Further information:
http://www.upenn.edu

More articles from Interdisciplinary Research:

nachricht Many muons: Imaging the underground with help from the cosmos
19.12.2016 | DOE/Pacific Northwest National Laboratory

nachricht Lego-like wall produces acoustic holograms
17.10.2016 | Duke University

All articles from Interdisciplinary Research >>>

The most recent press releases about innovation >>>

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

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

Im Focus: How to inflate a hardened concrete shell with a weight of 80 t

At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).

Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...

Im Focus: Bacterial Pac Man molecule snaps at sugar

Many pathogens use certain sugar compounds from their host to help conceal themselves against the immune system. Scientists at the University of Bonn have now, in cooperation with researchers at the University of York in the United Kingdom, analyzed the dynamics of a bacterial molecule that is involved in this process. They demonstrate that the protein grabs onto the sugar molecule with a Pac Man-like chewing motion and holds it until it can be used. Their results could help design therapeutics that could make the protein poorer at grabbing and holding and hence compromise the pathogen in the host. The study has now been published in “Biophysical Journal”.

The cells of the mouth, nose and intestinal mucosa produce large quantities of a chemical called sialic acid. Many bacteria possess a special transport system...

Im Focus: Newly proposed reference datasets improve weather satellite data quality

UMD, NOAA collaboration demonstrates suitability of in-orbit datasets for weather satellite calibration

"Traffic and weather, together on the hour!" blasts your local radio station, while your smartphone knows the weather halfway across the world. A network of...

Im Focus: Repairing defects in fiber-reinforced plastics more efficiently

Fiber-reinforced plastics (FRP) are frequently used in the aeronautic and automobile industry. However, the repair of workpieces made of these composite materials is often less profitable than exchanging the part. In order to increase the lifetime of FRP parts and to make them more eco-efficient, the Laser Zentrum Hannover e.V. (LZH) and the Apodius GmbH want to combine a new measuring device for fiber layer orientation with an innovative laser-based repair process.

Defects in FRP pieces may be production or operation-related. Whether or not repair is cost-effective depends on the geometry of the defective area, the tools...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

Nothing will happen without batteries making it happen!

05.01.2017 | Event News

 
Latest News

Multiregional brain on a chip

16.01.2017 | Power and Electrical Engineering

New technology enables 5-D imaging in live animals, humans

16.01.2017 | Information Technology

Researchers develop environmentally friendly soy air filter

16.01.2017 | Power and Electrical Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>