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 Bergamotene - alluring and lethal for Manduca sexta
21.04.2017 | Max-Planck-Institut für chemische Ökologie

nachricht How to color a lizard: From biology to mathematics
13.04.2017 | Université de Genève

All articles from Interdisciplinary Research >>>

The most recent press releases about innovation >>>

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

Im Focus: Carbon Nanotubes Turn Electrical Current into Light-emitting Quasi-particles

Strong light-matter coupling in these semiconducting tubes may hold the key to electrically pumped lasers

Light-matter quasi-particles can be generated electrically in semiconducting carbon nanotubes. Material scientists and physicists from Heidelberg University...

Im Focus: Flexible proximity sensor creates smart surfaces

Fraunhofer IPA has developed a proximity sensor made from silicone and carbon nanotubes (CNT) which detects objects and determines their position. The materials and printing process used mean that the sensor is extremely flexible, economical and can be used for large surfaces. Industry and research partners can use and further develop this innovation straight away.

At first glance, the proximity sensor appears to be nothing special: a thin, elastic layer of silicone onto which black square surfaces are printed, but these...

Im Focus: 3-D scanning with water

3-D shape acquisition using water displacement as the shape sensor for the reconstruction of complex objects

A global team of computer scientists and engineers have developed an innovative technique that more completely reconstructs challenging 3D objects. An ancient...

Im Focus: Manipulating Electron Spins Without Loss of Information

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...

Im Focus: The proton precisely weighted

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...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Clash of Realities 2017: Registration now open. International Conference at TH Köln

26.07.2017 | Event News

Closing the Sustainability Circle: Protection of Food with Biobased Materials

21.07.2017 | Event News

»We are bringing Additive Manufacturing to SMEs«

19.07.2017 | Event News

 
Latest News

CCNY physicists master unexplored electron property

26.07.2017 | Physics and Astronomy

Molecular microscopy illuminates molecular motor motion

26.07.2017 | Life Sciences

Large-Mouthed Fish Was Top Predator After Mass Extinction

26.07.2017 | Earth Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>