Navigation Links
Unusual protein modification involved in muscular dystrophy, cancer
Date:12/31/2009

With the discovery of a new type of chemical modification on an important muscle protein, a University of Iowa study improves understanding of certain muscular dystrophies and could potentially lead to new treatments for the conditions.

The findings, which appear in the Jan. 1, 2010, issue of the journal Science, may also have implications for detecting metastasizing cancer cells.

After they are initially made, most proteins are modified through the addition of sugar chains, fats or other chemical groups. These modifications can completely change how a protein works and where it is located in the body. Disruption of these modifications can alter protein function, too, and can lead to disease.

The UI study focused on dystroglycan, a cell membrane protein that is disrupted in many forms of muscular dystrophy. Normal dystroglycan is modified with a unique sugar chain that allows the protein to "glue" muscle membranes to the basal lamina -- a tough layer of extracellular proteins. This arrangement reinforces the fragile muscle membrane and prevents small tears that occur naturally from expanding and damaging the membrane.

Recent work, including studies by the UI team, show that disrupting dystroglycan's ability to attach to the basal lamina causes congenital muscular dystrophies and also leads to cancer progression in epithelial cell cancer. In these conditions, the dystroglycan sugar chain is incompletely or incorrectly assembled and the dystroglycan cannot bind tightly to laminin.

"Dystroglycan is a complex and unusual glycoprotein. It is heavily covered with many types of sugars. We wanted to know the shape and make up of the unique sugar chain that allows dystroglycan to bind to laminin," said study leader Kevin Campbell, Ph.D., professor and head of molecular physiology and biophysics at the UI Roy J. and Lucille A. Carver College of Medicine and a Howard Hughes Medical Institute investigator.

Lead study author Takako Yoshida-Moriguchi, Ph.D., a postdoctoral researcher in Campbell's lab, used a combination of biochemical methods and chemical and structure analysis to determine that a critical link within the sugar chain involves a phosphate group. This type of link is found in yeast and fungi but has not previously been found in higher organisms like mammals.

"This phosphate link is very unusual, which may explain why the actual structure of dystroglycan's laminin-binding sugar chain has been a mystery for many years despite the efforts of numerous research teams," said Campbell, who also holds the Roy J. Carver Chair of Physiology and Biophysics. "The findings help explain what is happening in congenital muscular dystrophies where the dystroglycan sugar chain is truncated and ends at the phosphate. The bare phosphate does not bind laminin; it has to be further modified."

Several enzymes are involved in building the sugar chain beyond the phosphate, and mutations in these enzymes are the cause of congenital muscular dystrophies.

"If we can discover the entire structure and make up of the sugar chain beyond the phosphate link, we might be able to target some of the enzymes involved in building the sugar chain, and thus, develop therapies to treat congenital muscular dystrophies," Campbell said.

In certain cancer cells, one of these enzymes, known as LARGE, also is suppressed. Campbell speculated that loss of LARGE activity produces dystroglycan that is unable to interact with the basal lamina, which makes the cancer cells more mobile and allows them to escape into the bloodstream. The study's findings could lead to new methods for tracking metastasizing cancer cells.


'/>"/>

Contact: Jennifer Brown
jennifer-l-brown@uiowa.edu
319-356-7124
University of Iowa
Source:Eurekalert

Related biology news :

1. Unusual microbial ropes grow slowly in cave lake
2. Properties of unusual virus revealed in research
3. Researchers study virus with unusual properties
4. Unusual use of toys in infancy a clue to later autism
5. Genes and nutrition influence caste in unusual species of harvester ant
6. Popular apple variety harbors unusual cell growth
7. Unusual fish-eating dinosaur had crocodile-like skull
8. Biologists find unusual plant gene: abstinence by mutual consent
9. Scientists learn structure of enzyme in unusual virus
10. Molecular chaperone keeps bacterial proteins from slow-dancing to destruction
11. BBS proteins shown to run an export business that protects cilia
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:4/5/2017)... , April 5, 2017  The Allen Institute for ... Cell Explorer: a one-of-a-kind portal and dynamic digital window ... imaging data, the first application of deep learning to ... stem cell lines and a growing suite of powerful ... for these and future publicly available resources created and ...
(Date:4/4/2017)... 2017   EyeLock LLC , a leader of ... States Patent and Trademark Office (USPTO) has issued U.S. ... of an iris image with a face image acquired ... company,s 45 th issued patent. ... given the multi-modal biometric capabilities that have recently come ...
(Date:3/30/2017)... , March 30, 2017 The research ... system for three-dimensional (3D) fingerprint identification by adopting ground breaking 3D ... a new realm of speed and accuracy for use in identification, ... an affordable cost. ... ...
Breaking Biology News(10 mins):
(Date:10/10/2017)... CA (PRWEB) , ... October ... ... a development-stage cancer-focused pharmaceutical company advancing targeted antibody-drug conjugate (ADC) therapeutics, today ... of targeted HPLN (Hybrid Polymerized Liposomal Nanoparticle), a technology developed in collaboration ...
(Date:10/10/2017)... 2017 International research firm Parks Associates announced today ... the TMA 2017 Annual Meeting , October 11 in ... home security market and how smart safety and security products impact the ... Parks Associates: Smart Home Devices: ... "The residential security market has experienced ...
(Date:10/10/2017)... ... October 10, 2017 , ... The Pittcon ... awards honoring scientists who have made outstanding contributions to analytical chemistry ... Pittcon 2018, the world’s leading conference and exposition for laboratory science, which will ...
(Date:10/9/2017)... ... October 09, 2017 , ... At its national board ... Stubbs, a professor in Harvard University’s Departments of Physics and Astronomy, has been selected ... member of the winning team for the 2015 Breakthrough Prize in Fundamental physics for ...
Breaking Biology Technology: