Featured Research

from universities, journals, and other organizations

Surprising culprit found in cell recycling defect: Protein ends up in the wrong place

Date:
February 20, 2014
Source:
Washington University in St. Louis
Summary:
To remain healthy, the body’s cells must properly manage their waste recycling centers. Problems with these compartments, known as lysosomes, lead to a number of debilitating and sometimes lethal conditions. An unusual cause of the lysosomal storage disorder called mucolipidosis III, has been identified, at least in a subset of patients. Unlike most genetic diseases that involve dysfunctional or missing proteins, the culprit is a normal protein that ends up in the wrong place.

To remain healthy, the body’s cells must properly manage their waste recycling centers. Problems with these compartments, known as lysosomes, lead to a number of debilitating and sometimes lethal conditions.

Related Articles


Reporting in the Proceedings of the National Academy of Sciences (PNAS), researchers at Washington University School of Medicine in St. Louis have identified an unusual cause of the lysosomal storage disorder called mucolipidosis III, at least in a subset of patients. This rare disorder causes skeletal and heart abnormalities and can result in a shortened lifespan. But unlike most genetic diseases that involve dysfunctional or missing proteins, the culprit is a normal protein that ends up in the wrong place.

“There is a lot of interest and study about how cells distribute proteins to the right parts of the cell,” said senior author Stuart A. Kornfeld, MD, PhD, the David C. and Betty Farrell Professor of Medicine. “Our study has identified one of the few examples of a genetic disease caused by the misplacement of a protein. The protein functions just fine. It just doesn’t stay in the right place.”

The right place, in this case, is the Golgi apparatus, the cell’s protein packaging center. The protein in question – phosphotransferase – normally resides in the Golgi, where its job is to attach address labels to proteins bound for the lysosome. There are 60 such lysosomal proteins, and all of them must be properly labeled if they are to end up in a lysosome, where they recycle waste.

Kornfeld and his colleagues, including first author Eline van Meel, PhD, postdoctoral research associate, showed that the phosphotransferase protein responsible for adding the address label starts out in the Golgi as it should, but seems to lack the signal to keep it there.

“Under normal circumstances, the phosphotransferase moves up through the Golgi, but then it’s recaptured and sent back,” Kornfeld said. “Our study shows that the mutant phosphotransferase moves up but is not recaptured. Ironically, the phosphotransferase that escapes the Golgi ends up in the lysosomes, where it is degraded.”

Because phosphotransferase gradually wanders away from the Golgi, a low level of lysosomal enzymes end up being properly addressed, but at perhaps 20 percent of the normal amount.

“In many lysosomal storage disorders, such as Tay-Sachs or Gaucher’s disease, only one out of the 60 enzymes is missing from the lysosome,” Kornfeld said. “But the mislocalization of phosphotranferase causes the misdirection of all 60 lysosomal enzymes.”

While the errant phosphotransferase ends up being degraded in the lysosome, the resulting misdirected lysosomal proteins end up in the bloodstream. As a result, children with this disorder have lysosomal proteins in their blood at levels 10 to 20 times higher than normal. But because some get to the lysosome at a low level, people with mucolipidosis III don’t have the most severe form of the disease.

“Type III patients live into adulthood, but they’re very impaired,” said Kornfeld. “They have joint and heart problems and have trouble walking. In the most severe form, type II, there is zero activity of phosphotransferase. None of the 60 enzymes are properly tagged, so these patients’ lysosomes are empty. Children with type II usually die by age 10.”

Having implicated wayward phosphotransferase in this lysosomal storage disorder, Kornfeld and his colleagues are investigating what goes wrong that allows it to escape the Golgi.

“We think there must be some protein in the cell that recognizes phosphotransferase when it gets to the end of the Golgi, binds it and takes it back,” said Kornfeld. “Now we’re trying to understand how that works.”


Story Source:

The above story is based on materials provided by Washington University in St. Louis. The original article was written by Julia Evangelou Strait. Note: Materials may be edited for content and length.


Journal Reference:

  1. E. van Meel, Y. Qian, S. A. Kornfeld. Mislocalization of phosphotransferase as a cause of mucolipidosis III. Proceedings of the National Academy of Sciences, 2014; DOI: 10.1073/pnas.1401417111

Cite This Page:

Washington University in St. Louis. "Surprising culprit found in cell recycling defect: Protein ends up in the wrong place." ScienceDaily. ScienceDaily, 20 February 2014. <www.sciencedaily.com/releases/2014/02/140220132002.htm>.
Washington University in St. Louis. (2014, February 20). Surprising culprit found in cell recycling defect: Protein ends up in the wrong place. ScienceDaily. Retrieved March 29, 2015 from www.sciencedaily.com/releases/2014/02/140220132002.htm
Washington University in St. Louis. "Surprising culprit found in cell recycling defect: Protein ends up in the wrong place." ScienceDaily. www.sciencedaily.com/releases/2014/02/140220132002.htm (accessed March 29, 2015).

Share This


More From ScienceDaily



More Plants & Animals News

Sunday, March 29, 2015

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Raw: Lioness Has Rare Five-Cub Litter

Raw: Lioness Has Rare Five-Cub Litter

AP (Mar. 27, 2015) — A lioness in Pakistan has given birth to five cubs, twice the usual size of a litter. Queen gave birth to two other cubs just nine months ago. (March 27) Video provided by AP
Powered by NewsLook.com
Jockey Motion Tracking Reveals Racing Prowess

Jockey Motion Tracking Reveals Racing Prowess

Reuters - Innovations Video Online (Mar. 26, 2015) — Using motion tracking technology, researchers from the Royal Veterinary College (RVC) are trying to establish an optimum horse riding style to train junior jockeys, as well as enhance safety, health and well-being of both racehorses and jockeys. Matthew Stock reports. Video provided by Reuters
Powered by NewsLook.com
Bear Cubs Tumble for the Media

Bear Cubs Tumble for the Media

Reuters - Light News Video Online (Mar. 26, 2015) — Two Andean bear cubs are unveiled at the U.S. National Zoo in Washington, D.C. Alicia Powell reports. Video provided by Reuters
Powered by NewsLook.com
Botswana Talks to End Illegal Wildlife Trade

Botswana Talks to End Illegal Wildlife Trade

AFP (Mar. 25, 2015) — Experts are gathering in Botswana to try to end the illegal wildlife trade that is decimating populations of elephants, rhinos and other threatened species. Duration: 01:05 Video provided by AFP
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

 

Plants & Animals

Earth & Climate

Fossils & Ruins

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