Myosin Motor Proteins in Health and Disease
We are studying the role(s) of myosin motor proteins in intracellular transport of organelles and vesicles, and in cell migration and cytokinesis. In humans at least 40 different myosins operate to control and drive these complex range of motile and transport processes. Each myosin is composed of a motor domain that uses the energy released from ATP hydrolysis to drive along actin filament tracks around the cell and a tail domain that binds cargo and targets it to specific cellular locations. We have focused on myosin VI, which unlike all the other myosins so far characterised moves in the reverse direction along actin filaments and therefore has unique molecular properties and intracellular functions. We have localized myosin VI in membrane ruffles, at the Golgi complex, in clathrin coated pits and vesicles, at the centrosome and in the mid-body during cytokinesis and have shown that it is involved in a wide variety of intracellular processes such as endocytosis, secretion, maintenance of Golgi morphology, cell movement and cell division. The multiple roles of myosin VI in these membrane transport pathways are mediated by interaction of its specific C-terminal tail domain with a host of distinct binding partners which are currently one of our main areas of research. Mutations or the absence of myosin VI have been linked to such diverse pathological processes as deafness, cardiomyopathy, neurodegeneration and cancer. Our long term aim is therefore to establish the precise intracellular functions of myosin VI so as to allow us to develop therapeutic strategies to combat or alleviate these pathological disorders.
Funding:
- The Wellcome Trust
- Cancer Research UK
Group members
- Sue Arden
- Margarita Chibalina
- Claudia Puri
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