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Multi-disciplinary Penn research identifies protein required for cell movement
Date:8/12/2013

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."

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Contact: Katherine Unger Baillie
kbaillie@upenn.edu
215-898-9194
University of Pennsylvania
Source:Eurekalert

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