The goal of this work is to undestand the mechanisms responsible for the organization of cytoplasmic microtubules (MT) in living cells. An increasing body of evidence indicates that MT motors that use MTs as 'rails' for the transport of organelles and chromosomes can in turn organize MTs themselves into elaborate arrays. The goal of the proposed research is to examine the role of a minus-end MT motor Ned in the formation of the mitotic spindle, an intracellular MT-based machinery responsible for the segregation of chromosomes during mitosis. A hypothesis will be tested that Ned plays dual role in the spindle formation by focusing MTs into spindle poles and generating the MT sliding force that pulls the poles together. A combination of biochemical, molecular, and imaging approaches will be used to test whether Ned can indeed induce MT sliding and to examine the mechanism of Ned-dependent formation of MT asters. The results of this study will answer a long-standing question about the role of MT motors in the spindle morphogenesis and also provide a foundation for the development of new cancer therapeutics based on the targeting mitotic MT motors.
| Oladipo, Abiola; Cowan, Ann; Rodionov, Vladimir (2007) Microtubule motor Ncd induces sliding of microtubules in vivo. Mol Biol Cell 18:3601-6 |
