Rainer Prohaska (1943-2022)

Rainer Prohaska, a distinguished scientist, a much-valued PI and mentor of many students and co-workers, an appreciated colleague and beloved husband and father of two children passed away in 2022. He was a professor of Biochemistry at the Medical University of Vienna and crucially contributed to our knowledge of the structure and function of stomatin, a protein with a peculiar membrane association, which is involved in the regulation of subcellular lipid/membrane processes and is abundant in lipid rafts of the erythrocyte plasma membrane and numerous other cell types (Figure 1). Rainer's passion for chemistry already awoke when he was still a child. His mother had to refurbish his nursery room twice after exciting experiments with explosive chemicals had run out of control. She therefore sent him to a chemical-technical college to ensure a more supervised access to science. Rainer studied chemistry at the University of Vienna and did his PhD in the laboratory of Hans Tuppy, the godfather of biochemistry in Austria renowned for his participation in insulin sequencing in Frederik Sanger's laboratory. In the legacy of Karl Landsteiner, Tuppy's laboratory was at that time focusing on the molecular characterization of the human blood group system. This brought Rainer in contact with the world of membrane proteins (and their modifications) and the amazing red blood cells, which both sparked a lifelong fascination and determined his future career. During his time abroad as postdoc, Rainer extended his study on the blood group system in Heinz Furthmayr's lab at the Yale University School of Medicine and worked on components of the complement system at the MRC Immunochemistry Unit of the University of Oxford. Back home in Vienna, Rainer set up his own lab at the Department of Biochemistry of the University of Vienna (later Medical University of Vienna) where he continued working far beyond his official retirement. His early career as PI was dedicated to investigations on the complex Rhesus system, until three home-made monoclonal antibodies, which all recognized the same protein in the “band 7 region” of erythrocyte membrane protein extracts, changed his scientific interest: it was soon evident that this band did not correspond to one of the Rhesus antigens but rather to a new abundant erythrocyte membrane protein, which he sequenced and published as “human erythrocyte band 7 integral membrane protein.”1 Nearly at the same time this protein was also characterized by Johnson (published as “band 7.2b protein”) and by Stewart who introduced the now common name “stomatin” because of its strongly reduced abundance in the erythrocytes of hereditary stomatocytosis patients. Rainer has since been focused on the elucidation of the peculiar properties of this novel membrane protein. Similar to caveolin, stomatin has a monotopic structure2 with (the only) one hydrophobic stretch being inserted into the membrane bilayer and both the N-terminus and the bulk C-terminal part facing the cytosol (Figure 1). His studies identified the amino acid residues that are prone to reversible phosphorylation and palmitoylation modifications3 and revealed the sequence motifs that mediate homo-oligomerization are required for association with detergent-resistant membranes (lipid rafts)4 and bind cholesterol in a noncovalent manner, respectively.5 Rainer early on realized that these characteristics qualify stomatin and other stomatin-like proteins as regulators at the lipid–membrane protein interface. His studies to elucidate this enigmatic function contributed to our understanding of various cell biological aspects: (i) the co-existence of various types of lipid rafts at the erythrocyte membrane6, 7 that likely segregate in processes, for example, malaria invasion or vesicle shedding during long-term storage of packed red blood cells; (ii) the variable subcellular localization of stomatin (plasma membrane, endocytic vesicles, exocytic vesicles, lipid bodies,…)8, 9 depending on cell type and cell state implicating a role in subcellular membrane organization; (iii) the promiscuous association of stomatin with membrane channels, transporters, facilitators and cytoskeletal proteins10 suggesting a function in modulating processes at and exchange through the membrane bilayer.11, 12 Rainer was a passionate scientist and his profound knowledge, creativity, curiosity and perseverance allowed him to address topics that were not easily accessible by common scientific routes. Even in the last days of his life, he proposed a hypothesis related to stomatin and suggested a respective experiment. He was concise, focused, and calm—as he has always been when addressing a scientific question. The committed scientist was only the one side of Rainer; the other side was his impressive being expressed by his gentle and noble personality, his readiness to help, and his constant commitment for humanity. Born in war-shuttered Vienna and grown up in the depressing and negating climate of postwar Austria, Rainer was strongly attracted by the spirit of freedom and peace that thrived in the 60s in England where he frequently commuted in this time for “regeneration” (as he phrased it). Throughout his life he was a peaceful fighter for human dignity and against any form of bigotry, arrogance, and discrimination. He was an environmentalist all along, never owning or driving a car by himself. The love for and of his family, his friends, and his research surely has helped to overcome and completely regenerate from an aggressive form of leukemia in 2008. Rainer was a “class act” and is and will be sadly missed by all who got to know him.