Research
Microtubules are intracellular dynamic polymers made up of evolutionarily conserved polymorphic αβ-tubulin heterodimers and a large number of microtubule-associated proteins. Microtubules are required for vital processes in eukaryotic cells including mitosis, meiosis, maintenance of cell shape and intracellular transport. Various signaling molecules interact with microtubule components, and microtubules are critical for spatial organization of signal transduction. Several populations of microtubules of different composition, stability and properties carry out these essential functions in cells. Post-translational modifications of tubulins play an important role in the determination of microtubule properties. Organization of microtubular networks in cells is controlled by microtubule organizing centres (MTOCs). One of the key components of MTOCs is the γ-tubulin. Gamma-tubulin is a highly conserved minor member of the tubulin family that interacts with γ-tubulin komplex proteins to create small and large complexes that participace in microtubule nucleation. In addition, γ-tubulin may participate in other functions, such as cell cycle progression or dynamics of the microtubule ends. Regulations of these functions are just about beginning to be understood.
The long-term research program of the laboratory includes the study of structure-function relationships of microtubule proteins and their interactions with other cytoskeletal elements in cells under normal and pathological conditions. To this end the research group has used immunological approaches and prepared a panel of monoclonal antibodies that made it possible to contribute to the structural mapping of tubulin dimers, analyse their posttranslational modifications and identify the microtubule-interacting proteins. In recent years the research efforts concentrated towards the elucidation of the molecular mechanisms governing the microtubule nucleation and dynamics, and the role of γ-tubulin in these processes. It has been shown that soluble γ-tubulin is posttranslationally modified, interacts with tubulin heterodimers and forms complexes with protein tyrosine kinases. Experimental evidence has been provided that the properties of γ-tubulin change during differentiation events, and that γ-tubulin is not universal nucleator of microtubules. It could also be demonstrated that γ-tubulin is present in membrane-associated complexes and in nuclei. Nuclear γ-tubulin associates with tumor suppressor protein C53 and modulates DNA damage G2/M checkpoint activation.
Current work focuses on the understanding of the modulation of microtubule properties by signal transduction molecules, the function of γ-tubulin forms, and molecular and functional characterization of regulators of microtubule nucleation. To address these questions, techniques of molecular biology, biochemistry and immunology are being used, as well as a variety of advanced microscopic techniques, including live cell imaging and quantification of microtubule plus end dynamics.
