Microtubule motors, cytoskeletal organization and cell polarity

PROJECT SUMMARY The overall goal of our work is to understand how microtubules and microtubule motors define the structure of cytoplasm and interphase cell polarization. We and others have established, that in addition to the “canonical” function of moving cargo along microtubules, kinesin-1 and cytoplasmic dynein can move cytoskeletal filaments themselves thus organizing the cytoplasm and polarizing cells. We will use three biological models in this proposal (i) Drosophila oocytes, where transport of microtubules by kinesin-1 drives bulk rotation of cytoplasm for localization of polarity determinants and cytoplasmic dynein responsible for the bulk cargo transport in nurse cells and from nurse cells to the oocyte; (ii) cells with elongated processes (neurons and terminal cells of the trachea of Drosophila) where the movement of parallel or antiparallel microtubule arrays is involved in the generation of processes and extension of the intracellular lumen in terminal cells; (iii) dynamics of intermediate filaments in mammalian cells that is defined by microtubules and microtubule motors. Discoveries of new mechanisms that we hope to generate will be useful for development of new treatments of neurodegenerative disorders and the defects of egg development in humans.