Breaking new ground at the
Neuromuscular Junction with mTORC1
To move our bodies as we wish is something that is often taken for granted; we expect our muscles to collaborate based on the signals we send. However, for many individuals this is not a given as the prevalence of neuromuscular diseases (NMD) are on the rise. In addition, as the average lifespan continues to expand, increased age is a significant contributor to muscle weakness which compromises the mobility of many.
The Neuromuscular Junction
For muscles to contract and thus allow us to move as we wish, to maintain our balance, or elicit reflexes to unpleasant stimuli, they communicate with nerve cells via neuromuscular connections. The crucial location of the communication between these two cells is where the presynaptic nerve terminal meets the postsynaptic receptors in the motor endplate of skeletal muscle fibers. The specialized synapse just described is denoted the neuromuscular junction. Maintenance of the motor endplate on the side of the muscle is vital in order for re-innervation to occur, after for example damage from disease or atrophy caused by ageing has taken place.
A protein complex called mTORC1
New research conducted at the University of Basel’s Biozentrum led by Markus Rüegg has shed new light on the role of a particular protein complex in the muscles’ response to upstream nerve damage, an area which had not been studied in such detail before. Previously, this protein complex called mTORC1, has been known for its importance in promoting the growth of muscles as well as the self-cleaning processes of these cells. The new insights provided by Rüegg’s research team points out an important and delicate balance between mTORC1 and its upstream kinase PKB/Akt in the preservation and maintenance of the motor endplate after nerve damage has occurred.
The importance of a balanced activation of both mTORC1 and PKB/Akt
Once nerve damage has taken place, both mTORC1 and PKB/Akt are activated. Using mouse models, the team discovered that in the instance that mTORC1 is activated too strongly, it inhibits the activation of PKB/Akt, which results in that the neuromuscular endplate is lost, and with that the functional capability of the particular muscle fiber. In the article which was published in Nature Communications, the first author Perrine Castets explains that this increased knowledge of the importance of a balanced activation of both mTORC1 and PKB/Akt can aid in the development of new approaches intended to counteract both the structural changes induced by NMD as well as ageing.
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