Navigation Links
Unusual alliances enable movement
Date:2/8/2012

Augusta, Ga. Some unusual alliances are necessary for you to wiggle your fingers, researchers report.

Understanding those relationships should enable better treatment of neuromuscular diseases, such as myasthenia gravis, which prevent muscles from taking orders from your brain, said Dr. Lin Mei, Director of the Institute of Molecular Medicine and Genetics at Georgia Health Sciences University.

During development, neurons in the spinal cord reach out to muscle fibers to form a direct line of communication called the neuromuscular junction. Once complete, motor neurons send chemical messengers, called acetylcholine, via that junction so you can text, walk or breathe.

As a first step in laying down the junction, motor neurons release the protein agrin, which reaches out to LRP4, a protein on the muscle cell surface. This activates MuSK, an enzyme that supports the clustering of receptors on the muscle cell surface that will enable communication between the brain and muscle. The precise alignment between the neuron and muscle cell that occurs during development ensures there is no confusion about what the brain is telling the muscle to do.

A missing piece was how agrin and LRP4 get together.

A study published in the journal Genes & Development shows that in the space between the neuron and its muscle cell, agrin and LRP4 first form two diverse work teams: each team has one agrin and one LRP4. The two teams then merge to form a four-molecule complex essential to MuSK activation and to the clustering of receptors that will receive the chemical messenger acetylcholine on the muscle cell.

It was expected that the two agrins would get together first then prompt the LRP4s to merge. "This is very novel," said Mei, and an important finding in efforts to intervene in diseases that attack the neuromuscular junction.

Mei and Dr. Rongsheng Jin, neuroscientist and structural biologist in the Del E. Webb Neuroscience, Aging and Stem Cell Research Center at Sanford-Burnham Medical Research Institute in La Jolla, Calif., are co-corresponding authors of the study.

Myasthenia gravis, which paralyzes previously healthy individuals, targets these protein workers. The condition, which can run in families, likely results from a process called mimicry in which the immune system starts making antibodies to the workers, which it confuses with a previous viral or bacterial infection. The majority of patients have antibodies to acetylcholine receptors and a smaller percentage have antibodies to MuSK. Most recently, GHSU researchers also helped identify LRP4 as an antibody target.

The scientists already are looking at the impact of the antibodies on the LRP4 complex. Understanding its unique structure is essential to designing drugs that could one day block such attacks. "Prior to this we had no idea how they interacted," Mei said.

In addition to providing new information on muscle diseases, this study might also have a far-reaching ripple effect in the field of neuroscience.

"This is just the beginning," says Jin. "Now that we know more about how signals are transferred during the formation of neuromuscular junctions, we can start looking at how a similar system might work in brain synapses and how it malfunctions in neurodegenerative conditions like Alzheimer's and Parkinson's diseases. If we can figure out how to trigger the formation of new brain synapses, maintain old synapses, or simply slow their disappearance, we'd be much better equipped to prevent or treat these diseases."

To reveal the novel mechanism, researchers used a technique known as X-ray crystallography, which produces 3-D "pictures" of protein at the atomic level using powerful X-ray beams.


'/>"/>

Contact: Toni Baker
tbaker@georgiahealth.edu
706-721-4421
Georgia Health Sciences University
Source:Eurekalert  

Related biology news :

1. Bonobos unusual success story
2. New study to test unusual hypothesis on beta brainwaves
3. Dairy farmer finds unusual forage grass
4. Clue to unusual drug-resistant breast cancers found
5. Expedition to Mid-Cayman Rise identifies unusual variety of deep sea vents
6. Unusual rhino beetle behavior discovered
7. Virus infection may trigger unusual immune cells to attack nerves in multiple sclerosis
8. Unusual protein modification involved in muscular dystrophy, cancer
9. Unusual microbial ropes grow slowly in cave lake
10. Properties of unusual virus revealed in research
11. Researchers study virus with unusual properties
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Unusual alliances enable movement
(Date:6/22/2016)... 2016   Acuant , the leading ... has partnered with RightCrowd ® to ... Management, Self-Service Kiosks and Continuous Workforce Assurance. ... functional enhancements to existing physical access control ... with an automated ID verification and authentication ...
(Date:6/20/2016)... , June 20, 2016 Securus Technologies, ... technology solutions for public safety, investigation, corrections and ... prisons involved, it has secured the final acceptance ... facilities for Managed Access Systems (MAS) installed. Furthermore, ... facilities to be installed by October, 2016. MAS ...
(Date:6/9/2016)... 9, 2016  Perkotek an innovation leader in attendance control systems is proud to ... hours, for employers to make sure the right employees are actually signing in, and ... ... ... ...
Breaking Biology News(10 mins):
(Date:6/24/2016)... ... June 24, 2016 , ... Researchers at the Universita Politecnica delle Marche ... with peritoneal or pleural mesothelioma. Their findings are the subject of a new article ... Diagnostic biomarkers are signposts in the blood, lung fluid or tissue of mesothelioma patients ...
(Date:6/23/2016)... 23, 2016 A person commits a crime, and ... to track the criminal down. An outbreak of ... Drug Administration (FDA) uses DNA evidence to track down the ... Sound far-fetched? It,s not. The FDA has increasingly used a ... of foodborne illnesses. Put as simply as possible, whole genome ...
(Date:6/23/2016)... SAN FRANCISCO , June 23, 2016   ... it has secured $1 million in debt financing from ... to ramp up automation and to advance its drug ... for its new facility. "SVB has been ... goes beyond the services a traditional bank would provide," ...
(Date:6/23/2016)... NEWPORT BEACH, Calif. , June 23, 2016 /PRNewswire/ ... offering new biological discoveries to the medical community, has ... and co-founder Matthew Nunez . "We ... provide us with the capital we need to meet ... funding will essentially provide us the runway to complete ...
Breaking Biology Technology: