Biology

Dr. Ashim Rai
Protein Acrobatics Lab, Department of Genetics, Cell Biology, and Development, University of Minnesota, USA

Abstract:

Cytoskeletal motor proteins transport cargoes in a spatially and temporally regulated manner to organize the cell interior. Regulation of motor transport by the cargo interface occurs through adaptor proteins that act as a bridge between the motor and the cargo interface. Although cargo adaptors have been known to affect motor structure and function, the role of the functional context in which the adaptor-mediated regulation of motor transport happens is not understood. The functional context is defined by the local cytoskeletal organization and the turnover rates of the motor to the cargo. Here, we have dissected the structure-function regulation of Myosin VI by endocytic cargo adaptor proteins Dab2 and GIPC that are involved in Myosin VI transport in diverse functional contexts inside the cell. Using an array of approaches at both single-molecule and ensemble level, we have examined the multiplexed effect of adaptor binding on Myosin VI structure, motility, force generation, cytoskeletal reorganization, and collective transport. Our results show that Dab2 and GIPC confer differential structural and functional adaptations to Myosin VI to enable cargo transport in diverse cellular contexts and actin environments.