TAK1 regulates the activation of multiple signaling pathways in skeletal muscle. However, the role and mechanisms by which TAK1 regulates skeletal muscle mass remain less understood. Now, a mouse study by scientists from the University of Houston (UH) demonstrates how TAK1 regulates skeletal muscle mass.
Their findings are published in the journal Nature Communications in a paper titled, “Supraphysiological activation of TAK1 promotes skeletal muscle growth and mitigates neurogenic atrophy.”
“Skeletal muscle mass is regulated through coordinated activation of multiple signaling pathways,” the researchers wrote. “TAK1 signalosome has been found to be activated in various conditions of muscle atrophy and hypertrophy. However, the role and mechanisms by which TAK1 regulates skeletal muscle mass remain less understood. Here, we demonstrate that supraphysiological activation of TAK1 in skeletal muscle of adult mice stimulates translational machinery, protein synthesis, and myofiber growth.
“We demonstrate that supraphysiological activation of TAK1 in skeletal muscle stimulates translational machinery, protein synthesis, and myofiber growth,” explained Ashok Kumar, the UH College of Pharmacy Else and Philip Hargrove endowed professor and chair, department of pharmacological and pharmaceutical sciences.
Using genetic approaches, the researchers demonstrated that TAK1 is indispensable for maintaining healthy neuromuscular junctions, which are involved in transmitting nerve impulses to skeletal muscle and allowing muscle contractions.
“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 Anirban Roy, PhD, research assistant professor of pharmacology at the University of Houston.
“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,” added Roy.
The researchers are looking to investigate whether the activation of TAK1 using small molecules is sufficient to promote muscle growth and prevent atrophy in the elderly and various disease states. Their findings pave the way for future studies focused on neuromuscular disorders.