Centrosomes are unique subcellular organelles involved in the organization of cytoarchitecture from yeast to man. Ass microtubule organizing centers (MTOCs), centrosomes are directly or indirectly involved in numerous fundamental cell processes including cell replication, cell migration, directed organelle traffic and maintenance of cell shape and polarity. Thus, understanding centrosome function will impact our understanding of cancer, metastasis, chemotaxis and early development. The long term goals of this work are to understand centrosome composition, the molecular basis of microtubule nucleation and the biochemical regulation of centrosome function. Taking advantage of the unique properties of Spisula solidissima oocytes, methods have been developed to: 1) induce cell cycle-specific centrosome maturation in vitro; 2) isolate centrosomes from distinct phases of the oocyte cell cycle, 3) disassemble and reassemble a centrosome's ability to organize microtubules, 4) generate antibodies which specifically recognize centrosome proteins, and 5) isolate genes that code for centrosome proteins. Funds are requested to continue work to identify proteins required for centrosome assembly and centrosome- dependent microtubule nucleation. Centrosome protein phosphorylation will be studied to identify protein kinase enzymes that control centrosomes, to begin to unravel the mechanisms by which protein phosphorylation regulates centrosome function. This proposal will complete work to identify important centrosome proteins, and begin to exploit this unique in vitro system to purify molecules that regulate centrosome function.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
Research Project (R01)
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Cell Development and Function Integrated Review Group (CDF)
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Deatherage, James F
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University of Kansas Lawrence
Schools of Arts and Sciences
United States
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Shang, Wen; Crone, Donna E; Yang, Hoichang et al. (2009) Using centrosome fragments in the directed assembly of microtubules. J Nanosci Nanotechnol 9:871-5
DiMaio, Michael A; Mikhailov, Alexei; Rieder, Conly L et al. (2009) The small organic compound HMN-176 delays satisfaction of the spindle assembly checkpoint by inhibiting centrosome-dependent microtubule nucleation. Mol Cancer Ther 8:592-601
Sankaran, Satish; Crone, Donna E; Palazzo, Robert E et al. (2007) Aurora-A kinase regulates breast cancer associated gene 1 inhibition of centrosome-dependent microtubule nucleation. Cancer Res 67:11186-94
Sankaran, Satish; Crone, Donna E; Palazzo, Robert E et al. (2007) BRCA1 regulates gamma-tubulin binding to centrosomes. Cancer Biol Ther 6:1853-7
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Schnackenberg, B J; Palazzo, R E (2001) Reconstitution of centrosome microtubule nucleation in Spisula. Methods Cell Biol 67:149-65
Nilsson, H; Steffen, W; Palazzo, R E (2001) In vitro reconstitution of fish melanophore pigment aggregation. Cell Motil Cytoskeleton 48:1-10
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Palazzo, R E; Vogel, J M; Schnackenberg, B J et al. (2000) Centrosome maturation. Curr Top Dev Biol 49:449-70

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