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Protein-dependent 'switch' regulates intracellular trafficking in epithelial cells
Date:12/11/2007

ns" work by moving their cargoes along filamentous tracks, known as microtubules. "When everything is working right, appropriate surface markers end up where they need to go. However, in rare cases, mix-ups occur, and they can be devastating -- causing sickness not only of cells but of the organ of which those cells are a part," Dr. Kreitzer explains.

Scientists have spent decades investigating vesicular trafficking. But the exact role for each of the 41 members of the kinesin family has remained unclear.

In their study, Dr. Kreitzer's team focused on four different cell membrane proteins. They knew these proteins were destined to be packed up and transported via microtubules to key spots on the surface of the epithelial cell.

"We knew kinesins played a role in all that -- but did it matter which kinesin"" Dr. Kreitzer says.

To find out, her team inhibited specifically the activity of a series of different kinesins, in turn, then watched to see what happened.

"We discovered something exciting: that the journey a particular surface marker makes depends on a specific member of the kinesin family. What worked for one protein did not work for the others," Dr. Kreitzer says. "That tells us that there's real 'selectivity' going on. It also tells us that the type of kinesin selected is a key piece of information determining where a particular surface protein will go."

"That's great news for drug development, because it means that we might use this selectivity to target the appropriate motor protein whenever a specific pathway goes wrong," Dr. Kreitzer says. "That could potentially mean more effective, targeted therapies with fewer side effects."

The team also discovered that selectivity of the motor for its cargo (passenger) switches after the epithelial cell has differentiated and fully matured. "When we worked with immature, developing cells, the type of kinesin used is clearly different," Dr. Kreitzer poin
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Contact: Andrew Klein
ank2017@med.cornell.edu
212-821-0560
New York- Presbyterian Hospital/Weill Cornell Medical Center/Weill Cornell Medical College
Source:Eurekalert

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