Experiments show hypothesis of microtubule steering accurate

Posted: January 23, 2014 at 7:46 pm

7 hours ago This is a model for maintenance of proper microtubule polarity in dendrites. Polymerizing microtubules entering junctions encounter existing static filaments. A complex consisting of end-binding protein 1 (EB1) and a kinesin molecular motor binds to the tip of the growing filament and moves along the static filament to co-align the filaments and maintain proper uniform orientation. The present work demonstrates that an EB1-kinesin complex is able to steer a growing microtubule in this manner without the requirement for any other cellular components. Credit: William Hancock, Penn State

Tiny protein motors in cells can steer microtubules in the right direction through branching nerve cell structures, according to Penn State researchers who used laboratory experiments to test a model of how these cellular information highways stay organized in living cells.

"We proposed a model of how it works in vivo, in the living cell," said Melissa Rolls, associate professor of biochemistry and molecular biology. "But because of the complexity of the living cells, we couldn't tell if the model was possible."

Rolls then collaborated with William O. Hancock, professor of biomedical engineering, who was already working on the tiny kinesin motors that move materials throughout the cell, to test the model in the laboratory, in vitro.

"Kinesins are little machines that use chemical energy to generate mechanical forces sufficient to carry materials through the cell," said Hancock.

Cells produce enzymes, proteins and signaling chemicals in the center of the cell, and these materials are then moved to other cell areas by kinesin motors. Dendrites in nerves cells are very long, and motors need to transport molecules relatively long distances on microtubules that are constantly forming and dissolving within the cell. Because dendrites branch, the researchers wondered how the microtubules themselves move in the right direction.

Working with Yalei Chen, graduate student in cell and developmental biology in the Huck Institutes of the Life Sciences, the researchers found that kinesin motors can not only transport molecules along the tubules, but can redirect the ends of the tubules to enter the proper branch of the dendrite. They report their findings online today (Jan. 23) in Current Biology.

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In the laboratory, the researchers grew microtubules under the microscope and used protein engineering to attach a kinesin motor to EB1a protein that binds to the growing end of microtubules.

"One of the reasons we thought the model might not work is that the molecule EB1 grabs the plus end of the microtubule very loosely," said Rolls. "We were unsure how something so dynamic could hold the forces, but it does."

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Experiments show hypothesis of microtubule steering accurate

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