The myosin VI interactome: the role of motor cargo/adaptor complexes and ubiquitin-binding during selective autophagy

点击翻译按钮获取中文摘要

A significant proportion of our ageing population is affected by the late onset of neurodegenerative disorders such as Alzheimer's, motor neuron or Parkinson's diseases. A better understanding of what causes these neurodegenerative diseases could lead to new therapeutic and preventive strategies or could at least improve the quality of life of the affected patients. More and more research now suggests that motor neuron disease and some forms of dementia are linked to defects in a cellular pathway that is used to digest abnormal proteins or defective parts of the cell. These defects can lead to an accumulation of these protein as large clumps, which may clog up the transport of essential cargo along nerves in our limbs and eventually cause the nerve cells to die. Our research is focused on the special molecular motor protein myosin VI, which drives cargo along tracks in the opposite direction to all other motors to specific sites in the cell, rather like a train running along a railway network to its specific destinations. The cargo is hooked up to the motor with the help of specific adaptor proteins that we have identified in our research. New results now show that this motor protein is present on protein lumps found in nerve cells from patients that died from Alzheimer's disease. Furthermore, it was recently shown that mistakes (mutations) in the protein optineurin, which links myosin VI to specific cargos, causes an inherited form of motor neuron disease. We will thus explore whether myosin VI and optineurin move and dispose of these toxic protein lumps and prevent their accumulation to avoid the death of nerve cells and subsequent neurodegenerative diseases.We thus hope to identify the precise roles of myosin VI and its adaptor proteins in the pathway that is important for clearance of protein aggregates to keep the nerve cells healthy. This will open up new areas of research that may guide future clinical studies and the development of potential diagnostic tools and possible therapeutic strategies.