Navigation Links
Strong communication between brain and muscle requires both having the protein LRP4
Date:7/11/2012

AUGUSTA, Ga. Communication between the brain and muscle must be strong for us to eat, breathe or walk. Now scientists have found that a protein known to be on the surface of muscle cells must be present in both tissues to ensure the conversation is robust.

Scientists at the Medical College of Georgia at Georgia Health Sciences University have shown that without LRP4 in muscle cells and neurons, communication between the two cells types is inefficient and short-lived.

Problems with the protein appear to contribute to disabling disorders such as myasthenia gravis and other forms of muscular dystrophy. The MCG scientists reported finding antibodies to LRP4 in the blood of about 2 percent of patients with muscle-degenerating myasthenia gravis in Archives of Neurology earlier this year.

Scientists know that LRP4 plays an important role in the muscle cell, where it receives cues from the brain cell that it's time to form the receptors that will be enable ongoing communication between the two, said Dr. Lin Mei, Director of the GHSU Institute of Molecular Medicine and Genetics and corresponding author of the study in the journal Neuron.

However when Dr. Haitao Wu deleted LRP4 just from muscle cells, a connection albeit a weak one still formed between muscle and brain cells. The mice survived several days during which they experienced some of the same muscle weakness as patients with myasthenia gravis. "That's against the dogma," Mei said. "If LRP4 is essential only in the muscle cells, how could the mice survive?" When they totally eliminated LRP4, neuromuscular junctions never formed and the mice didn't survive.

Additional evidence suggests that LRP4 in the neurons is vital, said Wu, postdoctoral fellow and the study's first author. "When we knocked out the LRP4 gene in the muscles, there was some redundant function coming from the motor neuron, like a rescue attempt," he said. They documented the neuron reaching out to share LRP4 with the muscle cell. Unfortunately, the gesture was not sufficient.

"The nerve does not get the stop signal," Mei said, referencing images of too-long neurons that never got the message from the muscle that they have gone far enough. When they cut the elongated nerves, they found they didn't contain enough vesicles, little packages of chemical messengers that are the hallmark of brain cell communication. On the receiving end, muscle cells developed receptors that were too small and too few hence, the tenuous communication network. "When LRP4 in the muscle is taken out, not surprisingly, the muscle has some kind of a problem," Mei said. "What was very surprising was that the motor neurons also have problems."

"The talk between motor neurons and muscle cells is very critical to the synapse formation and the very precise action between the two," Wu said. Mei's lab earlier established that the conversation goes both ways.

The scientists believe about 60 percent of the LRP4 comes from muscle cells, about 20 percent from brain cells which helps explain why the brain's effort to share is insufficient and the remainder from cells in spaces between the two. In addition to better explaining nerve-muscle communication, the scientists hope their findings will eventually enable gene therapy that delivers LRP4 to bolster insufficient levels in patients.

Other early and key players in establishing nerve-muscle conversation include agrin, a protein that motor neurons release to direct construction of the synapse, a sort of telephone line between the nerve and muscle. MuSK on the muscle cell surface initiates critical internal cell talk so synapses can form and receptors that enable specific commands will cluster at just the right spot.

Mei's lab reported in Neuron in 2008 that agrin starts talking with LRP4 on the muscle cell surface, then recruits the enzyme MuSK to join the conversation. LRP4 and MuSK become major components of the receptor needed for the muscle cell to receive the message agrin is sending.

The agrin-MuSK signaling pathway has been implicated in muscular dystrophy, a group of genetic diseases that lead to loss of muscle control because of problems with neurons, muscle cells and/or their communication. Some reports have implicated a mutant MuSK as a cause of muscular dystrophy and autoantibodies (antibodies the body makes against itself) to MuSK have been found in the blood of some patients.


'/>"/>
Contact: Greg Deriso
gderiso@georgiahealth.edu
706-721-7134
Georgia Health Sciences University
Source:Eurekalert  

Related medicine news :

1. Symptomatic behaviour in childhood strongly predicts psychiatric treatment as a young adult
2. Military Marriages Stay Strong in Face of Challenges: Study
3. Does dinner make a strong family, or does a strong family make dinner?
4. Gastroenterology, CGH maintain strong 2011 impact factors
5. Unusual protein helps regulate key cell communication pathway
6. Listening in, researchers learn about end-of-life communication
7. Study links teamwork, communication with quality of nursing home care
8. Version 2.0 of Award-Winning Proloquo2Go App for iPhone, iPad & iPod touch Speeds Up Communication, Adds New Voices and Customization Options
9. Hospitals communication during residency matching may put stress on OB-GYN doctors-in-training
10. EP Global Communications, Inc. Achieves Shareholder Approval for Restructuring and Signs Definitive Restructuring Agreement
11. Study finds significant skull differences between closely linked groups
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Strong communication between brain and muscle requires both having the protein LRP4
(Date:4/29/2017)... ... April 29, 2017 , ... TransDark is a set ... one video to the next without having to set a single keyframe in ... to enhance your video production. , TransDark features dynamic transitions that momentarily splits the ...
(Date:4/28/2017)... (PRWEB) , ... April 28, 2017 , ... An April 24th article on ... stunning 180 pounds with the help of a weight loss surgery. The woman, declaring “I ... skin that have been left following her dramatic weight loss. Dr. Feiz & Associates notes ...
(Date:4/28/2017)... , ... April 28, 2017 , ... Beginning in 2017, ... their formulas. This begins with the popular ClearLungs Extra Strength formula. To ensure that ... the formula in the following ways:, , Removal of the ...
(Date:4/28/2017)... ... April 28, 2017 , ... Ushio America ... lamps offer an instant energy-saving solution for F32T8 fluorescent lamps on most instant-start ... ballasts. These 50,000 hour rated lamps utilize the existing electronic ballast, saving labor ...
(Date:4/28/2017)... ... April 28, 2017 , ... From ... College of Urgent Care Medicine will host industry leaders for the annual spring ... help those in the industry adapt to the issues currently affecting urgent care ...
Breaking Medicine News(10 mins):
(Date:4/20/2017)... 20, 2017  Cogentix Medical, Inc. (NASDAQ: CGNT), ... the Urology, Uro/Gyn and Gynecology markets with innovative ... has joined the Company as Senior Vice President, ... position, Mr. Keswani will report directly to ... "Our organization is delighted that Ash has joined ...
(Date:4/20/2017)... , April 20, 2017  RXi Pharmaceuticals Corporation ... therapeutics that address significant unmet medical needs, today ... the Company,s consumer product development program, based on ... Society for Investigative Dermatology (SID) 76 th ... and promote the sciences relevant to skin health ...
(Date:4/20/2017)... , April 20, 2017  AbbVie (NYSE: ... 99 percent (n=145/146) of chronic hepatitis C virus ... 5 or 6 and compensated cirrhosis (Child-Pugh A) ... (SVR 12 ) with its investigational, pan-genotypic regimen ... rates were seen following 12 weeks of G/P ...
Breaking Medicine Technology: