Final Report Summary - NANO-ISLANDS (NANOSCALE ANALYSIS OF PROTEIN ISLANDS ON LYMPHOCYTES)
A major question is how nano-islands are generated and maintained on the dynamic plasma membrane. Our finding that caveolin and CD20 are important for the stability of the class-specific nano-island provided a first answer to these questions. Furthermore, we showed that a B cell-specific disturbance of the nano-island organization results in a deregulation of the immune system and autoimmunity. Concerning the generation of nano-islands, we still are working on the nano-island sorting code. Helpful for this would be an efficient proximity proteomics analysis and a catalogue of the composition of all nano-islands on the B lymphocyte membrane, one of the goals that we could not achieve during the ERC funding period. However, we are currently collaborating with a membrane proteomics group and hope to reach this goal in the future. An important game changer for our work is the CRISPR/Cas9 technology that allows us to rapidly delete genes of a human B cell line. We have thus generated many mutant B cell lines and in combination with the Fab-PLA technology this allows us to identify components that are critical for the nano-island organization and stability. Concerning the final goal of our ERC project we studied the alteration of the nano-island organization on several human B cell tumors. We found that B cell chronic lymphocytic leukemia (B-CLL) is associated with an altered nano-island composition and organization resembling more that of activated than of resting B lymphocytes. Furthermore, we identified a novel pro-survival module inside a nano-island that is required for the competitive fitness of a human Burkitt lymphoma cell line. We think that, in the long run, studies of the nano-islands organization on normal or diseased human cells will have a major impact on medical diagnostics and practice.