Cell Cycle Regulation of Microtubule Assembly

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The intent of this study is to identify the macromolecules involved in the regulation of microtubule assembly during the interphase-to- mitosis transition in developing sea urchin embryos. Unfertilized sea urchin eggs are arrested at G1 of the first mitotic cycle and have few, if any assembled microtubules despite a large pool of tubulin subunits. Following fertilization microtubules of the first cleavage mitotic apparatus are synchronously assembled. Therefore the developing sea urchin embryo can be viewed as an inducible model system for studying the regulation of microtubule assembly. It has been recently discovered that interphase-arrested egg cells contain two novel inhibitors of microtubule assembly- a minus-end inhibitor and a pH-dependent plus-end inhibitor. The goal of the proposed research is to isolate and characterize these unique factors during the cell cycle. Preliminary experiments with such diverse sources as sea urchin eggs, surf clam oocytes, mouse B16 cultured melanoma cells, squid optic lobe and mammalian brain tissue suggest that these negative control factors may exist in all eukaryotic cells, particularly where cytoplasmic microtubules are rapidly assembled and disassembled in a controlled manner during the cell cycle. The interconversion of mitotic and interphase microtubule arrays during the cell cycle is a fundamental problem of cellular morphogenesis. The process is of obvious importance for cell division but also for developmental processes such as neuronal growth and plasticity. These studies are expected to increase our understanding of fundamental mechanisms whereby microtubule assembly is regulated in the living cell.