When we're active and doing exercise, we can build muscle as well as supply muscle cells with oxygen, maintaining their function and keeping them healthy. But if we're laid up in bed for long periods of time, not using our muscles for anything, the muscle cells can start to shrink, or atrophy. Skeletal muscle mass is controlled by a complex set of pathways, and scientists have found that a complex called the TAK1 signalosome is involved. Now, researchers have revealed more about how TAK1, which is also known to be involved in immune signaling, regulates the mass of skeletal muscle. The findings have been reported in Nature Communications.
This study indicated that when TAK1 is activated in skeletal muscle cells, it promotes protein synthesis, and the growth of myofibers. TAK1 has already been found to play a role in signaling pathways including MAPK kinase and non-canonical TGF-β signalling. TAK1 can also activate the NF-κB transcription factor.
When TAK1 was eliminated in skeletal muscles in a mouse model, there was muscle wasting in the mice as well as mitochondrial dysfunction and an increase in cell death, known as autophagy. TAK1 was necessary for the maintenance of neuromuscular junctions, where signals from nerves meet muscle, enabling movement.
“Our findings demonstrate that targeted inactivation of TAK1 causes derangement of neuromuscular junctions and severe muscle wasting, very similar to muscle wasting observed during nerve damage, aging and cancer cachexia. We have also identified a novel interplay between TAK1 and BMP (Bone Morphogenetic Protein) signaling pathway that promotes muscle growth,” said first study author Anirban Roy, PhD, a research assistant professor at the University of Houston.
While there are ways for healthy people to increase muscle mass, loss of muscle can accompany disease. The researchers found that when excessive TAK1 activation was triggered in skeletal muscle, the researchers found that it prevented the excessive loss of muscle that can occur when nerves are damaged.
The study has suggested that TAK1 is important to both the hypertrophy and atrophy of muscle.
Loss of muscle mass is a health complication during aging and in many terminal illnesses, and this work could help scientists prevent to treat that loss. “Recognizing the impact of TAK1 signaling in supporting muscle growth, our research opens up new avenues to develop therapies for these and many other pathological conditions and improve quality of life,” said Roy.