Mechanosensory kinases of the muscle sarcomere: the titin-like family of myofilaments

Friday 17 October 2014, 1.00PM

Speaker(s): Dr Olga Mayans, Liverpool University

Abtract

Mechanical stimulation is critical for the development of the muscle tissue, which undergoes constant remodeling in adaptation to mechanical demand. This mechano-feedback impacts both cardiac and skeletal muscle and has deep implications for the socio-economics of human health in modern societies. The giant proteins of the titin family form elastic filaments embedded within the sarcomere. These proteins are now being regarded as stretch-sensing molecules that integrate the response of muscle to mechanical stress. They contain a highly conserved kinase domain flanked by regulatory segments that undergo conformational deformations during muscle function. Mounting evidence suggests that structural changes in these segments regulate both kinase activity and the recruitment of sarcomeric proteins to kinase-based signallosomes that interconnect mechanosensing with gene expression pathways in the myofibril. Our laboratory studies the atomic structure, catalytic and tensile properties of cytoskeletal kinases from this family using recombinant samples in vitro.Our recent data have revealed a rich functional diversity across titin-like kinases regarding their function as active catalyzers and/or transient scaffolds that participate in signaling by modulating interactions to regulatory proteins. Evolutionary segregation within the family opens now new avenues for the pharmacological regulation of muscle function.

Host: Dr Belinda Bullard

Location: The Dianna Bowles Lecture Theatre (KO18)

Admission: Open

Email: anna.oconnell@york.ac.uk