Control of amino acid transporter endocytosis & degradation

It is clear that cells in our body need to eat to grow and divide. Surprisingly it is not understood how cells stop to eat when they are no longer growing. How cells regulate the acquisition of nutrients such as glucose, amino acids and fatty acids is a fundamental question in biology. These nutrients are basic building blocks for the synthesis of proteins and lipids, and their uptake must be synchronized with cell growth and proliferation to maintain tissue homeostasis and organismal health. In this research project, we focus on the molecular mechanism by which human cells control the improt of amino acids through amino acid transporters (AATs) at the plasma membrane (PM). Cells that are stimulated by growth factors, increase cellular amino acid uptake to grow and proliferate. Conversely, cells that stop to proliferate, exit the cell cycle and enter quiescence. Entry into quiescence is accompanied by a reduction in cell size, and by reduced protein synthesis. Quiescent cells also reduce the import of amino acids. Surprisingly, the molecular mechanism that allow quiescent cells to reduce the uptake of amino acids are unclear. This presents a major knowledge gap in understanding how cells control amino acid uptake. To fill this knowledge gap, we aim to identify and characterize the molecular mechanisms that are required to down-regulated amino acid uptake in human cells entering quiescence. Answering these questions will advance our understanding of the molecular mechanism that adjust amino acid import in proliferating and quiescence cells. This would be a major step forward with general implications for the regulation of cellular nutrient acquisition and help to explain how cells control what - and how much - they eat.