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

NEW YORK (Dec. 10, 2007) -- With findings highlighted on a recent cover of Developmental Cell, researchers at Weill Cornell Medical College in New York City have shed important new light on key trafficking mechanisms within epithelial cells. Epithelial cells line the outside of nearly all organs.

Specifically, the team has discovered a molecular "switch" in developed epithelial cells that selects from a large family of "motor proteins," called kinesins. Each kinesin facilitates the transport of specific surface markers from production sites inside the cell to their ultimate home on the cell's surface.

"Not only are many more kinesins present in cells than previously thought, but their selectivity helps direct which packages of surface proteins are transported, as well as their ultimate destinations," explains lead researcher Dr. Geri Kreitzer, assistant professor in the department of cell and developmental biology at Weill Cornell Medical College.

"Breakdown in these types of intracellular trafficking pathways is a serious contributing factor to many diseases ranging from cystic fibrosis to cancer," Dr. Kreitzer continues. "So, a better understanding of processes directed by the specific kinesin family members marks a big step forward in developing therapeutics that might someday treat or cure these illnesses. By targeting the individual motors rather than the tracks along which they all move (a current approach used to treat some types of cancer), we could bypass some of the effects on global cellular function that affect patients adversely."

Scientists have long understood the importance of kinesins in the life of the cell, she notes.

"These proteins are essentially 'trains' pulling packets (vesicles) of essential proteins and lipids from production sites in the heart of the cell up to areas on the outer surface, where the cell interacts with its environment," Dr. Kreitzer explains.

These kinesin "trains" 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 points out.

But how does the mature cell decide which kinesin to put to work on a particular transport mechanism"

"Right now, we just don't know," Dr. Kreitzer said. "Figuring out that molecular 'switch' is the next great frontier in this research."

For now, the study's findings hold promise for the study of devastating illnesses caused by defective placement of surface proteins, such as in cystic fibrosis, and even cancer.

"Right now, most chemotherapy targets the whole microtubule 'track' -- that's a really heavy-handed approach that typically affects the cell as a whole and causes serious side effects," notes Dr. Kreitzer.

"Imagine, though, that we could use what we now know about kinesins to target only the specific trafficking machinery that's gone awry," she says. "The result could be better, safer cancer care. And that paradigm holds true for a myriad of other diseases, as well."


'/>"/>

Contact: Andrew Klein
ank2017@med.cornell.edu
212-821-0560
New York- Presbyterian Hospital/Weill Cornell Medical Center/Weill Cornell Medical College
Source:Eurekalert

Related medicine news :

1. Schizophrenia Gene May Have On/Off Switch
2. Brain Switch Helps Doctors Deal With Patients Pain
3. Switching to MA Coverage Unlikely for Current Beneficiaries With MediGap or Medicare Only
4. Scientists Spot Eye Development Switch
5. A molecular switch is linked to a common breast cancer
6. Researchers identify unusual molecular switch for common form of advanced breast cancer
7. Cell Structure Helps Direct Cancer Gene Switch
8. Childrens Hospital researchers identify molecular switch that could save very young lives
9. Human C-reactive protein regulates myeloma tumor cell growth and survival
10. Insulin regulates the secretion of the antiaging hormome Klotho
11. New developments in biomarkers for epithelial ovarian cancer
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:9/26/2017)... ... 26, 2017 , ... Dr. Kovatis, is a Hospital for ... and Foot Section of the Department of Orthopedic Surgery at Hackensack University Medical ... UMC performing total ankle replacements. Because of this, Dr. Kovatis is often referred ...
(Date:9/26/2017)... Milford, PA (PRWEB) , ... September 26, 2017 , ... ... month in Chicago, called “The Magic of Fat,” revealed not only the latest about ... might prove to be an evolution in cosmetic medicine. , “Fat really is magical, ...
(Date:9/26/2017)... ... September 26, 2017 , ... The Organizing Committee ... tactical plans for Pittcon 2018. As of July 1, Adrian C. Michael, Ph.D. ... named vice president, Charles Gardner, (ChemImage Corporation) and selected chairs. , ...
(Date:9/26/2017)... ... September 26, 2017 , ... “Good Morning Sunshine!: Finding Strength and Comfort ... “Good Morning Sunshine!: Finding Strength and Comfort in God” is the creation of published ... Hays Sate University, who has worked at a local mental health center for over ...
(Date:9/26/2017)... ... ... “Sound of My Song”: an intriguing and thought-provoking on love, life, and ... retired teacher with a passion for music and ancestral history. , Published by ... loss, living with depression, and finding love through the journey. There is powerful imagery ...
Breaking Medicine News(10 mins):
(Date:9/19/2017)... , Sept. 19, 2017 HistoSonics, Inc., a venture-backed medical device company developing ... of targeted tissues, announced three leadership team developments today:   ... ... ... Veteran medical device executive Josh Stopek ...
(Date:9/18/2017)... KALAMAZOO, Mich. , Sept. 18, 2017  PMD ... OptiMed Specialty Pharmacy of Kalamazoo, Mich. ... strategic hub service that expedites and streamlines patient and ... Spiro PD 2.0, and wellness management services.  ... medical device used to measure lung function for a ...
(Date:9/13/2017)... Sept. 13, 2017   OrthoAtlanta has been named ... Football Host Committee (AFHC) for the 2018 College Football Playoff ... 2018, at Mercedes-Benz Stadium in Atlanta, Georgia ... AFHC "I,m In" campaign, participating in many activities leading up ... ...
Breaking Medicine Technology: