Cytoskeletal filament systems : assembly, regulation, and interplay in mammalian cells

Abstract: The cell represents the basic unit of structure and function for all life. The interior of a eukaryotic cell is organized by an extensive array of protein filaments – collectively referred to as the cytoskeleton. These filaments serve diverse essential functions, e.g. to provide mechanical resilience, facilitate intracellular transport, and enable cell polarization, locomotion and division. Here I have explored the mechanisms that regulate synthesis and assembly of two cytoskeletal filament systems – microtubules and septins – and how these interact in human cells. The present thesis is based on three principal discoveries. Firstly, we have found that the microtubule-destabilizing protein Op18/Stathmin also regulates synthesis of tubulin heterodimers, which are the building blocks for microtubules. Secondly, we have unraveled the general rules that govern assembly of mammalian septins into native polymerization-competent heterooligomers. Finally, our combined results point to a non-reciprocal interplay whereby interphase microtubules support a disc-like arrangement of septin filaments, which delineate static plasma membrane regions. I here discuss the physiological significance and implications of these findings.