Featured Research

from universities, journals, and other organizations

Certain Diseases, Birth Defects May Be Linked To Failure Of Protein Recycling System

Date:
December 26, 2007
Source:
Cincinnati Children's Hospital Medical Center
Summary:
A group of signaling proteins known as Wnt -- which help build the human body's skin, bone, muscle and other tissues -- depend on a complex delivery and recycling system to ensure their transport to tissue-building cell sites. Failure of this system may be a mechanism of cancer, heart disease or birth defects related to Wnt proteins, according to new research.

A group of signaling proteins known as Wnt - which help build the human body's skin, bone, muscle and other tissues - depend on a complex delivery and recycling system to ensure their transport to tissue-building cell sites, according to a study at Cincinnati Children's Hospital Medical Center. When the recycling system - the Retromer Complex - breaks down, the delivery of this specialized family of signaling proteins fails as their transport vehicle, a cargo receptor called Wntless (Wls) becomes unstable and is degraded. This important finding provides new insight into what may be a mechanism behind cancer, heart disease or birth defects related to Wnt proteins, researchers said.

Related Articles


Writing for the January 15, 2008 edition of Developmental Cell, researchers at Cincinnati Children's studied the critical role that a trafficking protein (called Vps35) has as the central assembly platform of the Retromer Complex. This complex is made up of trafficking proteins that act like cellular postmen to return a cargo receptor, Wls, from cellular compartments called endosomes to the Trans-Golgi Network. The network acts like a molecular clearing house - packaging and sorting proteins for targeted delivery - and the job of Wls is to deliver Wnt signaling proteins from Trans Golgi to their intended tissue-building sites. If the Retromer Complex fails to recycle Wls back to the Trans Golgi to do their job, it thwarts stable delivery of Wnt signaling proteins.

"We know secreted Wnt proteins play essential roles in many biological processes, including the development of diseases, but very little is known about the mechanisms by which Wnt processing and secretion are regulated," said Xinhua Lin, Ph.D., a researcher in the Division of Development Biology at Cincinnati Children's and senior author of the study. "Our main finding in this study is that the Retromer Complex is required for stable Wnt secretion, providing new insights into how certain diseases work."

In a series of experiments with genetically engineered cells from the fruit fly Drosophila, mice and humans, Dr. Lin and his colleagues mutated the Vps35 trafficking protein to compromise its central assembly role in the Retromer Complex, then observed the delivery cycle of Wnt proteins between the Trans-Golgi Network and targeted cell sites. In all three series, the compromised Retromer Complex resulted in Wnt protein accumulating in the Trans-Golgi Network and Wls cargo receptors being degraded instead of returning to the network and their job of delivering Wnt proteins.

"Although we propose that the Wls protein acts as a cargo receptor for Wnt signaling proteins, we need to conduct more experiments to further our understanding of this process, including how the Wls delivers Wnt from the Trans-Golgi," Dr. Lin said.

In their study, the researchers proposed a delivery cycle model where Wnt initially enters the Trans-Golgi Network and binds with the Wls cargo receptor, which then transports Wnt to targeted cell surfaces. Once Wls has delivered Wnt proteins, one of two things occurs, depending on whether the Retromer Complex is functioning normally. When working as designed, the Retromer Complex retrieves the spent Wls protein for return to the Trans-Golgi. When Retromer Complex breaks down, Wls cargo receptor is absorbed into the cell's lysosome, where it is digested and destroyed.

The study received funding support from partially by grants from the National Institutes of Health, the American Cancer Society, the American Heart Association and the March of Dimes.


Story Source:

The above story is based on materials provided by Cincinnati Children's Hospital Medical Center. Note: Materials may be edited for content and length.


Cite This Page:

Cincinnati Children's Hospital Medical Center. "Certain Diseases, Birth Defects May Be Linked To Failure Of Protein Recycling System." ScienceDaily. ScienceDaily, 26 December 2007. <www.sciencedaily.com/releases/2007/12/071220133443.htm>.
Cincinnati Children's Hospital Medical Center. (2007, December 26). Certain Diseases, Birth Defects May Be Linked To Failure Of Protein Recycling System. ScienceDaily. Retrieved December 22, 2014 from www.sciencedaily.com/releases/2007/12/071220133443.htm
Cincinnati Children's Hospital Medical Center. "Certain Diseases, Birth Defects May Be Linked To Failure Of Protein Recycling System." ScienceDaily. www.sciencedaily.com/releases/2007/12/071220133443.htm (accessed December 22, 2014).

Share This


More From ScienceDaily



More Health & Medicine News

Monday, December 22, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Touch-Free Smart Phone Empowers Mobility-Impaired

Touch-Free Smart Phone Empowers Mobility-Impaired

Reuters - Innovations Video Online (Dec. 21, 2014) A touch-free phone developed in Israel enables the mobility-impaired to operate smart phones with just a movement of the head. Suzannah Butcher reports. Video provided by Reuters
Powered by NewsLook.com
Earthworms Provide Cancer-Fighting Bacteria

Earthworms Provide Cancer-Fighting Bacteria

Reuters - Innovations Video Online (Dec. 21, 2014) Polish scientists isolate bacteria from earthworm intestines which they say may be used in antibiotics and cancer treatments. Suzannah Butcher reports. Video provided by Reuters
Powered by NewsLook.com
Existing Chemical Compounds Could Revive Failing Antibiotics, Says Danish Scientist

Existing Chemical Compounds Could Revive Failing Antibiotics, Says Danish Scientist

Reuters - Innovations Video Online (Dec. 21, 2014) A team of scientists led by Danish chemist Jorn Christensen says they have isolated two chemical compounds within an existing antipsychotic medication that could be used to help a range of failing antibiotics work against killer bacterial infections, such as Tuberculosis. Jim Drury went to meet him. Video provided by Reuters
Powered by NewsLook.com
Hugging It Out Could Help You Ward Off A Cold

Hugging It Out Could Help You Ward Off A Cold

Newsy (Dec. 21, 2014) Carnegie Mellon researchers found frequent hugs can help people avoid stress-related illnesses. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins