Lectures L9.1 Myosin VI in autophagy and

Myosins of class VI are unique actin based motor proteins that move cargo towards the minus ends of actin fila-ments. This motor interacts with a wide variety of adaptor proteins, which regulate cargo attachment and thus medi-ate the very specific intracellular functions of myosin VI in the endocytic and exocytic membrane trafficking pathways. These adaptor proteins may also act as molecular switches to regulate the on/off state of myosin VI. Our new data shows that myosin VI, in concert with its adaptor proteins optineurin, NDP52, T6BP and Tom1 plays a crucial role in autophagy, a degradative pathway that the cell uses to clear pathogens, damaged organelles and protein aggregates. The ESCRT-0 protein Tom1 is a novel myosin VI adaptor protein in mammalian cells that is involved in targeting of myosin VI to early endosomes. The loss of either myosin VI or Tom1 reduces delivery of endocytic cargo to autophagosomes, thereby preventing autophagosome maturation and autophagosome-lysosome fusion. As a consequence loss of myosin VI function caus-es a defect in autophagosome clearance and an accumula-tion of toxic protein aggregates in the cell. This observed dysfunction in autophagy may help to explain the profound astrogliosis phenotype that we observed in the myosin VI KO mouse brain. L9.2 The molecular basis of inherite