Structural and Functional Studies on MFSD1

A plethora of molecules crosses the cell membrane at any given time. The transport of molecules across this barrier is essential for a normal functioning of biological processes of the cell and of multicellular organisms. Nutrients, minerals and vitamins need to be taken up by cells while metabolic waste products need to be secreted to ensure a smooth functioning of the diverse biological tasks of cells. Besides the trafficking of molecules in and out of the cell, the transport must also be regulated within the cell between the different cell organelles and the cytoplasm to ensure that biological effects of the respective molecule are implemented in their assigned cellular compartment. However, most molecules are not able to cross the membrane. Thus, their transport depends on the presence of specific cell-membrane transporters allowing the respective molecules to be transported across the membrane. Membrane transporters are a group of membrane embedded proteins. Till recently these membrane transporters were hardly investigated due to their biochemical nature, which made them difficult to examine. However, due to the technological advance they are now subject to increased scientific interest and the function of these biologically immensely important group of proteins is being unraveled step-by-step. Our previous research endeavors disclosed physiologically important functions of the membrane transporter MFSD1, whose molecular function remains unknown. This membrane transporter regulates the transport of unknown molecules across the lysosomal membrane. Lysosomes are the cellular organelles required for degradation and recycling of macromolecules. Neither the structure, the mechanism of transport, nor the molecules transported by MFSD1 are known. With the funded project we are aiming to answer the mentioned open questions and thereby contribute to the general understanding of the transport of molecules across biological membranes. Furthermore, we are investigating the physiological relevance of MFSD1. It is known that a lack of this membrane transporter leads to a change in the phenotype on the organismal level (e.g., in the fruit fly and in mice) and on the cellular level (e.g., in tumor cells). As the involved transported molecules remain unknown, so do the underlying molecular mechanisms causing the phenotypic changes. By identifying the transported molecules, we will be able to investigate their contribution to the biological mechanisms responsible for the phenotypic changes observed. Summarizing, we will characterize the structure, mechanism of transport, and the identity of transported molecules of MFSD1. Building on these results we will continue to study the crucial role of MFSD1 and the respective transported molecules in additional, yet to be deciphered, biological pathways.