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
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Cincinnati Children's Hospital Medical Center