Identification of proteins involved in the establishment of the centrosome-independent, polarized microtubule cytoskeleton during differentiation of skeletal muscle cells

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Many microtubule-dependent processes require the arrangement of microtubules into suitable arrays. Generating microtubule patterns involves control of nucleation as well as regulated stabilization ob both microtubule ends. Typical tissue culture cells contain a radial array of microtubules emanating from the centrosome. But nucleation of microtubule assembly is not restricted to the centrosome and occurs frequently independent of a major MTOC in plants, fungi and differentiated animal cells. However, detailed mechanisms of non-centrosomal microtubule nucleation and anchorage are poorly understood. In the proposed project, mechanisms underlying microtubule rearrangements will be investigated in differentiating muscle cells. During myogenesis the centrosomes are eliminated while microtubules are nucleated on the nuclear surface. For several proteins, a relocation from the centrosome to the nuclear periphery was shown, but the mechanism of their recruitment remain to be discovered. Furthermore, previously isometric myoblasts elongate early during differentiation and parallel bundles of microtubules are formed between the poles of the developing myotubes, which most likely requires anchoring of plus ends at the cell poles as well as extensive microtubule stabilization along their length to promote the growth of long microtubule polymers. The major aim of this project is to describe the microtubule reorganization during myogenesis in detail and to identify and characterize proteins involved in the establishment of non-centrosomal nucleation sites and in the stabilization of parallel microtubules reaching the cell poles. This will help us to understand the mechanisms that are essential for the modulation of cell morphology during muscle cell differentiation and for the generation of centrosome-independent microtubule patterns in general.