Navigation Links
Certain diseases, birth defects may be linked to failure of protein recycling system

CINCINNATI - A group of signaling proteins known as Wnt - which help build the human bodys 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 Childrens 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.

Writing for the January 15, 2008 edition of Developmental Cell, researchers at Cincinnati Childrens 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 Childrens 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 cells lysosome, where it is digested and destroyed.


Contact: Nick Miller
Cincinnati Children's Hospital Medical Center

Related biology news :

1. Uncertainty drives the evolution of cooperative breeding in birds
2. Bilberry extract -- can it help prevent certain cancers?
3. New chimeric mouse model for human liver diseases, drug testing
4. Risk of common vaginal infection linked to preterm birth appears higher for blacks
5. Birth records hold pancreatic cancer clue
6. Researchers find evidence linking stress caused by the Sept. 11 disaster with low birth weights
7. Birth of an iceberg
8. The birth and death of dopamine neurons: A new model for neurodegeneration
9. Scientists show that mitochondrial DNA variants are linked to risk factors for type 2 diabetes
10. Protein chatter linked to cancer activation
11. Western diet linked to increased risk of colon cancer recurrence
Post Your Comments:
(Date:10/6/2015)... Track Group, Inc. (OTCQX: TRCK), a global ... a contract with the Virginia Department of Corrections to ... sentences under the Department,s oversight. Derek Cassell ... with the Virginia DOC will expand our footprint in ... position as a trusted leader in offender electronic monitoring ...
(Date:10/1/2015)... 1, 2015  Biometrics includes diverse set of ... characteristics, such as fingerprints, eye retinas, facial patterns, ... biometrics technology has been constantly increasing in ... years. In addition to the most prominent popular ... other means of biometric authentication are rapidly gaining ...
(Date:9/29/2015)... 2015 News facts: ... saving energy , Minimized design shrinks PC footprint ... Mode and embedded Fujitsu PalmSecure authentication enable enterprises to ... today shows that good things come in small packages, ... its enterprise desktop and mobile portfolio. Featuring workplace design ...
Breaking Biology News(10 mins):
(Date:10/13/2015)... , Oct. 13, 2015  Generex Biotechnology Corporation ( ... into a non-binding Letter of Intent (LOI) with MediTemp Ltd. ... developed a proprietary cooling technology designed to improve sperm quality ... the United States and three million men in ... and 44 diagnosed as infertile.  For 42% of those men, ...
(Date:10/13/2015)... ... , ... Proove Biosciences, a commercial and research leader ... Keck Medicine of the University of Southern California (USC) Pain Center to ... Research Clinical Objectives Linking Genotypic and Phenotypic Association with Pain Outcomes) is one ...
(Date:10/12/2015)... (PRWEB) , ... October 12, 2015 , ... Spirax Sarco, ... the release of the CSM-C 600 compact clean steam generator . This ... that meets the requirements of HTM2031, HTM2010, and EN285 standards. The CMS-C 600 ...
(Date:10/12/2015)... -- cell surface marker detection market is ... a new report by Grand View Research, Inc. This growth ... oncology diseases and other cell-associated disorders. --> cell ... 6.49 billion by 2022, according to a new report by ... attributed to rise in incidence of oncology diseases and other ...
Breaking Biology Technology: