Henning Wackerhage

Studying the mechanosensitive Hippo signal transduction network in skeletal muscle, the organ that generates the highest forces

PH 127

02.02.2018, 13:00

The Hippo signal transduction network was discovered as a result of tumour suppressor screens in the fly and studies that characterized the Yap/Taz-Tead1-4 transcription factor system. Together these studies revealed that the Hippo two kinase cascade inhibits Yap/Taz-Tead1-4-mediated transcription through inhibitory phosphorylation. In addition, Yap/Taz-Tead1-4 are also regulated by many other signalling modules including mechanical signals. Our research is focused on studying the Hippo signal transduction network in skeletal muscle where the Hippo proteins are expressed. We found that the Hippo effector YAP drives the proliferation of myoblasts and satellite cells (muscle stem cells) but prevents their differentiation. Persistent YAP hyperactivity in satellite cells causes embryonal rhabdomyosarcoma, a myoblast cancer. In differentiated muscle fibres, YAP can cause muscle fibre hypertrophy. A key question for our future research is: “Do the high forces generated during strength (resistance) exercise cause skeletal muscle hypertrophy through Hippo proteins and if so how are these forces sensed?”