Nav: Home

How neuromuscular connections are maintained after nerve lesions

July 25, 2019

After nerve injury, the protein complex mTORC1 takes over an important function in skeletal muscle to maintain the neuromuscular junction, the synapse between the nerve and muscle fiber. Researchers at the University of Basel's Biozentrum have now shown that the activation of mTORC1 must be tightly balanced for a proper response of the muscle to nerve injury. The study published in Nature Communications opens new insights into muscle weakness related to neuromuscular diseases or caused by ageing.

The protein complex mTORC1 promotes muscle growth and is important for the self-cleaning process of the muscle cells. The role of mTORC1 in skeletal muscle fibers in response to nerve injury has so far not been studied in detail. New insights have been provided by the research team led by Markus Rüegg at the Biozentrum of the University of Basel.

Function of mTORC1

Nerves and muscles in our body are connected by specialized synapses, called neuromuscular junctions, which transmit signals from the nerve to muscle fibers. If innervation is lost or interrupted by the injury of the nerve, muscles cannot contract anymore. However, to prepare the muscle for re-innervation by the nerve, the muscle component of the neuromuscular junction, the motor endplate, is maintained. Rüegg's research team has now more closely studied the function of mTORC1 and its upstream kinase PKB/Akt in the maintenance of the motor endplate after nerve injury using different mouse models.

The best known function of the PKB/Akt - mTORC1 signaling pathway is to promote muscle growth and the cellular self-cleaning process. «We have now been able to show that PKB/Akt and mTORC1 also play an important role in the maintenance of the neuromuscular endplate», explains Perrine Castets, first author of the study.

PKB/Akt - mTORC1 tightly balanced

After nerve damage, both PKB/Akt and mTORC1 get activated in muscle fibers. Rüegg's study demonstrates that mTORC1 should not be activated too strongly nor too little to ensure a proper response of the muscle. The underlying mechanism involves an mTORC1-dependent feedback onto the kinase PKB/Akt: «Should mTORC1 be too strongly activated, PKB/Akt is inhibited, resulting in the loss of the neuromuscular endplate. Balanced activation of both PKB/Akt and mTORC1 is required for the proper response of the muscle fiber», says Castets.

The newly described function of PKB/Akt and mTORC1 opens new perspective on how age-related muscle atrophy develops in humans. This is, likewise, induced through an alteration of neuromuscular endplates and possibly by over-activation of mTORC1. «Through this study, we now better understand the molecular mechanisms contributing to the maintenance of the neuromuscular junctions. Based on our results, we may be able to develop new approaches to potentially counteract age-related deficits and structural changes in order to better preserve the performance and functional capabilities of the muscles during ageing», says Rüegg.
-end-


University of Basel

Related Skeletal Muscle Articles:

Link between gut microbes & muscle growth suggests future approach to tackle muscle loss
Scientists led by NTU Singapore's Professor Sven Pettersson established a link between gut microbes and muscle growth and function -- a finding that could open new doors to interventions for age-related skeletal muscle loss.
Skeletal shapes key to rapid recognition of objects
In the blink of an eye, the human visual system can process an object, determining whether it's a cup or a sock within milliseconds, and with seemingly little effort.
Chloride-channel in muscle cells provides new insights for muscle diseases
Researchers from the University of Copenhagen have mapped the structure of an important channel in human muscle cells.
New skeletal disease found and explained
Researchers at Karolinska Institutet in Sweden have discovered a new and rare skeletal disease.
How diabetes causes muscle loss
Diabetes is associated with various health problems including decline in skeletal muscle mass.
Unintended side effects: antibiotic disruption of the gut microbiome dysregulates skeletal health
Diet and exercise regulate the accrual of bone mass, but some evidence suggests the microbiome may also play a role.
Central role of transforming growth factor type beta 1 in skeletal muscle dysfunctions
In this review we present the critical and recent antecedents regarding the mechanisms and cellular targets involved in the effects of TGF-β1 in the muscle, in pathological processes such as the inhibition of regeneration, fibrosis and atrophy.
Muscle-building proteins hold clues to ALS, muscle degeneration
Amyloid-like protein assemblies, long believed to be toxic and fuel diseases like ALS, have been found to play a key role in healthy muscle regeneration.
Unique type of skeletal stem cells found in 'resting zone' are actually hard at work
Skeletal stem cells are valuable because it's thought they can heal many types of bone injury, but they're difficult to find because researchers don't know exactly what they look like or where they live.
Skeletal stem cells regress when tasked with extensive regeneration
Adult mouse skeletal stem cells in the jaw revert to a more developmentally flexible state when called upon to regenerate large portions of bone and tissue, according to a study by researchers at the Stanford University School of Medicine.
More Skeletal Muscle News and Skeletal Muscle Current Events

Top Science Podcasts

We have hand picked the top science podcasts of 2019.
Now Playing: TED Radio Hour

Risk
Why do we revere risk-takers, even when their actions terrify us? Why are some better at taking risks than others? This hour, TED speakers explore the alluring, dangerous, and calculated sides of risk. Guests include professional rock climber Alex Honnold, economist Mariana Mazzucato, psychology researcher Kashfia Rahman, structural engineer and bridge designer Ian Firth, and risk intelligence expert Dylan Evans.
Now Playing: Science for the People

#540 Specialize? Or Generalize?
Ever been called a "jack of all trades, master of none"? The world loves to elevate specialists, people who drill deep into a single topic. Those people are great. But there's a place for generalists too, argues David Epstein. Jacks of all trades are often more successful than specialists. And he's got science to back it up. We talk with Epstein about his latest book, "Range: Why Generalists Triumph in a Specialized World".
Now Playing: Radiolab

Dolly Parton's America: Neon Moss
Today on Radiolab, we're bringing you the fourth episode of Jad's special series, Dolly Parton's America. In this episode, Jad goes back up the mountain to visit Dolly's actual Tennessee mountain home, where she tells stories about her first trips out of the holler. Back on the mountaintop, standing under the rain by the Little Pigeon River, the trip triggers memories of Jad's first visit to his father's childhood home, and opens the gateway to dizzying stories of music and migration. Support Radiolab today at Radiolab.org/donate.